Bioinformatics: Difference between revisions

Revision as of 12:00, 15 September 2024

Latest revision as of 08:24, 19 August 2025

(32 intermediate revisions by 24 users not shown)

Line 7:

[[Image:Genome viewer screenshot small.png|thumbnail|220px|Map of the human X chromosome (from the [[National Center for Biotechnology Information]] (NCBI) website)]]

'''Bioinformatics''' ({{IPAc-en|audio=en-us-bioinformatics.ogg|ˌ|b|aɪ|.|oʊ|ˌ|ɪ|n|f|ɚ|ˈ|m|æ|t|ɪ|k|s}}) is an [[interdisciplinary]] field of [[science]] that develops methods and [[Bioinformatics software|software tool]]s for understanding [[biological]] data, especially when the data sets are large and complex. Bioinformatics uses [[biology]], [[chemistry]], [[physics]], [[computer science]], [[data science]], [[computer programming]], [[information engineering]], [[mathematics]] and [[statistics]] to analyze and interpret [[biological data]]. The subsequentThis process of analyzingcan andsometimes interpreting data is oftenbe referred to as [[computational biology]], thoughhowever the distinction between the two terms is often disputed. To some, the term ''computational biology'' refers to building and using models of biological systems.

Computational, statistical, and computer programming techniques have been used for [[In silico|computer simulation]] analyses of biological queries. They include reused specific analysis "pipelines", particularly in the field of [[genomics]], such as by the identification of [[gene]]s and single [[nucleotide]] polymorphisms ([[SNPs]]). These pipelines are used to better understand the genetic basis of disease, unique adaptations, desirable properties (esp.especially in agricultural species), or differences between populations. Bioinformatics also includes [[proteomics]], which triesaims to understand the organizational principles within [[nucleic acid]] and [[protein]] sequences.<ref>{{cite web |vauthors=Lesk AM |date=26 July 2013 |title=Bioinformatics |url=https://www.britannica.com/science/bioinformatics |website=Encyclopaedia Britannica |access-date=17 April 2017 |archive-date=14 April 2021 |archive-url=https://web.archive.org/web/20210414103621/https://www.britannica.com/science/bioinformatics |url-status=live }}</ref>

Image and [[signal processing]] allow extraction of useful results from large amounts of raw data. In the field of genetics, itIt aids in sequencing and annotating genomes and their observed [[mutation]]s. Bioinformatics includes [[text mining]] of biological literature and the development of biological and gene [[ontologies]] to organize and query biological data. It also plays a role in the analysis of gene and protein expression and regulation. BioinformaticsBioinformatic tools aid in comparing, analyzing and, interpreting genetic and genomic data and more generally in the understanding of evolutionary aspects of molecular biology. At a more integrative level, it helps analyze and catalogue the biological pathways and networks that are an important part of [[systems biology]]. In [[structural biology]], it aids in the simulation and modeling of DNA,<ref name=":0">{{cite journal | vauthors = Sim AY, Minary P, Levitt M | title = Modeling nucleic acids | journal = Current Opinion in Structural Biology | volume = 22 | issue = 3 | pages = 273–8 | date = June 2012 | pmid = 22538125 | pmc = 4028509 | doi = 10.1016/j.sbi.2012.03.012 }}</ref> RNA,<ref name=":0" /><ref>{{cite journal | vauthors = Dawson WK, Maciejczyk M, Jankowska EJ, Bujnicki JM | title = Coarse-grained modeling of RNA 3D structure | journal = Methods | volume = 103 | pages = 138–56 | date = July 2016 | pmid = 27125734 | doi = 10.1016/j.ymeth.2016.04.026 | doi-access = free }}</ref> proteins<ref>{{cite journal | vauthors = Kmiecik S, Gront D, Kolinski M, Wieteska L, Dawid AE, Kolinski A | title = Coarse-Grained Protein Models and Their Applications | journal = Chemical Reviews | volume = 116 | issue = 14 | pages = 7898–936 | date = July 2016 | pmid = 27333362 | doi = 10.1021/acs.chemrev.6b00163 | doi-access = free }}</ref> as well as biomolecular interactions.<ref>{{cite book | vauthors = Wong KC |year=2016 |title=Computational Biology and Bioinformatics: Gene Regulation |publisher=CRC Press/Taylor & Francis Group |isbn=978-1-4987-2497-5 }}</ref><ref>{{cite journal | vauthors = Joyce AP, Zhang C, Bradley P, Havranek JJ | title = Structure-based modeling of protein: DNA specificity | journal = Briefings in Functional Genomics | volume = 14 | issue = 1 | pages = 39–49 | date = January 2015 | pmid = 25414269 | pmc = 4366589 | doi = 10.1093/bfgp/elu044 | doi-access = free }}</ref><ref>{{Cite book | vauthors = Spiga E, Degiacomi MT, Dal Peraro M |date=2014 |chapter=New Strategies for Integrative Dynamic Modeling of Macromolecular Assembly | veditors = Karabencheva-Christova T |title=Biomolecular Modelling and Simulations |series=Advances in Protein Chemistry and Structural Biology |volume=96 |pages=77–111 |publisher=Academic Press |doi=10.1016/bs.apcsb.2014.06.008 |pmid=25443955 |isbn=978-0-12-800013-7 }}</ref><ref>{{cite journal | vauthors = Ciemny M, Kurcinski M, Kamel K, Kolinski A, Alam N, Schueler-Furman O, Kmiecik S | title = Protein-peptide docking: opportunities and challenges | journal = Drug Discovery Today | volume = 23 | issue = 8 | pages = 1530–1537 | date = August 2018 | pmid = 29733895 | doi = 10.1016/j.drudis.2018.05.006 | doi-access = free }}</ref>

== History ==

The first definition of the term ''bioinformatics'' was coined by [[Paulien Hogeweg]] and [[Ben Hesper]] in 1970, to refer to the study of information processes in biotic systems.<ref>{{cite journal |last1=Ouzounis |first1=C. A. |last2=Valencia |first2=A. |date=2003 |title=Early bioinformatics: the birth of a discipline—a personal view |journal=Bioinformatics |volume=19 |issue=17 |pages=2176–2190 | pmid=14630646 | doi=10.1093/bioinformatics/btg309| doi-access=free}}</ref><ref name="Hogeweg2011">{{cite journal |vauthors=Hogeweg P |title=The Roots of Bioinformatics in Theoretical Biology |journal=PLOS Computational Biology |volume=7 |issue=3 |pages=e1002021 |date=2011 |pmid=21483479 |pmc=3068925 | doi=10.1371/journal.pcbi.1002021 | bibcode = 2011PLSCB...7E2021H | doi-access = free }}</ref><ref>{{Cite journal| vauthors = Hesper B, Hogeweg P |year=1970|title=BIO-INFORMATICA: een werkconcept |trans-title=BIO-INFORMATICS: a working concept |language=nl |journal=Het Kameleon|volume=1 |issue=6| pages=28–29}}</ref><ref>{{cite arXiv |vauthors=Hesper B, Hogeweg P |eprint=2111.11832v1 |title=Bio-informatics: a working concept. A translation of "Bio-informatica: een werkconcept" by B. Hesper and P. Hogeweg |date=2021 |class=q-bio.OT}}</ref><ref>{{cite journal |vauthors = Hogeweg P |title=Simulating the growth of cellular forms |journal=Simulation |volume=31 |issue=3 |pages=90–96 |year=1978 |doi=10.1177/003754977803100305 |s2cid=61206099 }}</ref> This definition placed bioinformatics as a field parallel to [[biochemistry]] (the study of chemical processes in biological systems).<ref name="Hogeweg2011" />

Bioinformatics and computational biology involved the analysis of biological data, particularly DNA, RNA, and protein sequences. The field of bioinformatics experienced explosive growth starting in the mid-1990s, driven largely by the [[Human Genome Project]] and by rapid advances in DNA sequencing technology.{{cn|date=MayFebruary 20242025}}

Analyzing biological data to produce meaningful information involves writing and running software programs that use [[algorithm]]s from [[graph theory]], [[artificial intelligence]], [[soft computing]], [[data mining]], [[image processing]], and [[computer simulation]]. The algorithms in turn depend on theoretical foundations such as [[discrete mathematics]], [[control theory]], [[system theory]], [[information theory]], and [[statistics]].{{cn|date=May 2024}}

Line 65:

{{main|Gene prediction}}

In [[genomics]], [[Genome project#Genome annotation|annotation]] refers to the process of marking the stop and start regions of genes and other biological features in a sequenced DNA sequence. Many genomes are too large to be annotated by hand. As the rate of [[DNA sequencing|sequencing]] exceeds the rate of genome annotation, genome annotation has become the new bottleneck in bioinformatics.{{When|date=June 2023}}.

Genome annotation can be classified into three levels: the [[nucleotide]], protein, and process levels.

Line 75:

Understanding the function of genes and their products in the context of cellular and organismal physiology is the goal of process-level annotation. An obstacle of process-level annotation has been the inconsistency of terms used by different model systems. The Gene Ontology Consortium is helping to solve this problem.<ref>{{cite journal |title=Genome annotation: from sequence to biology |journal=Nature |year=2001 |doi=10.1038/35080529|last1=Stein |first1=Lincoln |volume=2 |issue=7 |pages=493–503 |pmid=11433356 |s2cid=12044602 }}</ref>

The first description of a comprehensive annotation system was published in 1995<ref name="pmid7542800" /> by [[The Institute for Genomic Research]], which performed the first complete sequencing and analysis of the genome of a free-living (non-[[symbiotic]]) organism, the bacterium ''[[Haemophilus influenzae]]''.<ref name="pmid7542800" /> The system identifies the genes encoding all proteins, transfer RNAs, ribosomal RNAs, in order to make initial functional assignments. The [[GeneMark]] program trained to find protein-coding genes in ''[[Haemophilus influenzae]]'' is constantly changing and improving.

Following the goals that the Human Genome Project left to achieve after its closure in 2003, the [[ENCODE]] project was developed by the [[National Human Genome Research Institute]]. This project is a collaborative data collection of the functional elements of the human genome that uses next-generation DNA-sequencing technologies and genomic tiling arrays, technologies able to automatically generate large amounts of data at a dramatically reduced per-base cost but with the same accuracy (base call error) and fidelity (assembly error).

==== Gene function prediction ====

While genome annotation is primarily based on sequence similarity (and thus [[Homology (biology)|homology]]), other properties of sequences can be used to predict the function of genes. In fact, most ''gene'' function prediction methods focus on ''protein'' sequences as they are more informative and more feature-rich. For instance, the distribution of hydrophobic [[amino acid]]s predicts [[Transmembrane ___domain|transmembrane segments]] in proteins. However, protein function prediction can also use external information such as gene (or protein) [[Gene expression|expression]] data, [[protein structure]], or [[protein-protein interactions]].<ref>{{cite journal | vauthors = Erdin S, Lisewski AM, Lichtarge O | title = Protein function prediction: towards integration of similarity metrics | journal = Current Opinion in Structural Biology | volume = 21 | issue = 2 | pages = 180–8 | date = April 2011 | pmid = 21353529 | pmc = 3120633 | doi = 10.1016/j.sbi.2011.02.001 }}</ref>

===Computational evolutionary biology===

Line 90:

* build complex computational [[population genetics]] models to predict the outcome of the system over time<ref>{{cite journal | vauthors = Carvajal-Rodríguez A | title = Simulation of genes and genomes forward in time | journal = Current Genomics | volume = 11 | issue = 1 | pages = 58–61 | date = March 2010 | pmid = 20808525 | pmc = 2851118 | doi = 10.2174/138920210790218007 }}</ref>

* track and share information on an increasingly large number of species and organisms

Future work endeavours to reconstruct the now more complex [[Evolutionary tree|tree of life]].{{according to whom|date=June 2020}}

===Comparative genomics===

Line 107 ⟶ 106:

{{main|Genome-wide association studies}}

As of 2013, the existence of efficient high-throughput next-generation sequencing technology allows for the identification of cause many different human disorders. Simple [[Mendelian inheritance]] has been observed for over 3,000 disorders that have been identified at the [[Online Mendelian Inheritance in Man]] database, but complex diseases are more difficult. Association studies have found many individual genetic regions that individually are weakly associated with complex diseases (such as [[infertility]],<ref name="Demerec1945">{{cite journal | vauthors = Aston KI | title = Genetic susceptibility to male infertility: news from genome-wide association studies | journal = Andrology | volume = 2 | issue = 3 | pages = 315–21 | date = May 2014 | pmid = 24574159 | doi = 10.1111/j.2047-2927.2014.00188.x | s2cid = 206007180 | doi-access = free }}</ref> [[breast cancer]]<ref name="Véron2013">{{cite journal | vauthors = Véron A, Blein S, Cox DG | title = Genome-wide association studies and the clinic: a focus on breast cancer | journal = Biomarkers in Medicine | volume = 8 | issue = 2 | pages = 287–96 | year = 2014 | pmid = 24521025 | doi = 10.2217/bmm.13.121 }}</ref> and [[Alzheimer's disease]]<ref name="Tosto2013">{{cite journal | vauthors = Tosto G, Reitz C | title = Genome-wide association studies in Alzheimer's disease: a review | journal = Current Neurology and Neuroscience Reports | volume = 13 | issue = 10 | pages = 381 | date = October 2013 | pmid = 23954969 | pmc = 3809844 | doi = 10.1007/s11910-013-0381-0 }}</ref>), rather than a single cause.<ref name="Londin2013">{{Cite book |vauthors=Londin E, Yadav P, Surrey S, Kricka LJ, Fortina P |chapter=Use of linkage analysis, genome-wide association studies, and next-generation sequencing in the identification of disease-causing mutations |title=Pharmacogenomics |volume=1015 |pages=127–46 |year=2013 |pmid=23824853 |doi=10.1007/978-1-62703-435-7_8 |isbn=978-1-62703-434-0 |series=Methods in Molecular Biology }}</ref><ref>{{cite journal | vauthors = Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA | title = Potential etiologic and functional implications of genome-wide association loci for human diseases and traits | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 23 | pages = 9362–7 | date = June 2009 | pmid = 19474294 | pmc = 2687147 | doi = 10.1073/pnas.0903103106 | doi-access = free | bibcode = 2009PNAS..106.9362H }}</ref> There are currently many challenges to using genes for diagnosis and treatment, such as how we don't know which genes are important, or how stable the choices an algorithm provides. <ref>{{Cite book | vauthors = Hall LO |title=2010 International Conference on System Science and Engineering |chapter=Finding the right genes for disease and prognosis prediction |date=2010 |pages=1–2 |doi=10.1109/ICSSE.2010.5551766|isbn=978-1-4244-6472-2 |s2cid=21622726 }}</ref>

Genome-wide association studies have successfully identified thousands of common genetic variants for complex diseases and traits; however, these common variants only explain a small fraction of heritability.<ref>{{cite journal |last1=Manolio |first1=Teri A. |last2=Collins |first2=Francis S. |last3=Cox |first3=Nancy J. |last4=Goldstein |first4=David B. |last5=Hindorff |first5=Lucia A. |last6=Hunter |first6=David J. |last7=McCarthy |first7=Mark I. |last8=Ramos |first8=Erin M. |last9=Cardon |first9=Lon R. |last10=Chakravarti |first10=Aravinda |last11=Cho |first11=Judy H. |last12=Guttmacher |first12=Alan E. |last13=Kong |first13=Augustine |last14=Kruglyak |first14=Leonid |last15=Mardis |first15=Elaine |last16=Rotimi |first16=Charles N. |last17=Slatkin |first17=Montgomery |last18=Valle |first18=David |last19=Whittemore |first19=Alice S. |last20=Boehnke |first20=Michael |last21=Clark |first21=Andrew G. |last22=Eichler |first22=Evan E. |last23=Gibson |first23=Greg |last24=Haines |first24=Jonathan L. |last25=Mackay |first25=Trudy F. C. |last26=McCarroll |first26=Steven A. |last27=Visscher |first27=Peter M. |title=Finding the missing heritability of complex diseases |journal=Nature |date=October 2009 |volume=461 |issue=7265 |pages=747–753 |doi=10.1038/nature08494|pmid=19812666 |pmc=2831613 |bibcode=2009Natur.461..747M }}</ref> [[rare functional variant|Rare variants]] may account for some of the [[missing heritability]].<ref>{{cite journal |last1=Wainschtein |first1=Pierrick |last2=Jain |first2=Deepti |last3=Zheng |first3=Zhili |last4=Aslibekyan |first4=Stella |last5=Becker |first5=Diane |last6=Bi |first6=Wenjian |last7=Brody |first7=Jennifer |last8=Carlson |first8=Jenna C. |last9=Correa |first9=Adolfo |last10=Du |first10=Margaret Mengmeng |last11=Fernandez-Rhodes |first11=Lindsay |last12=Ferrier |first12=Kendra R. |last13=Graff |first13=Misa |last14=Guo |first14=Xiuqing |last15=He |first15=Jiang |last16=Heard-Costa |first16=Nancy L. |last17=Highland |first17=Heather M. |last18=Hirschhorn |first18=Joel N. |last19=Howard-Claudio |first19=Candace M. |last20=Isasi |first20=Carmen R. |last21=Jackson |first21=Rebecca |last22=Jiang |first22=Jicai |last23=Joehanes |first23=Roby |last24=Justice |first24=Anne E. |last25=Kalyani |first25=Rita R. |last26=Kardia |first26=Sharon |last27=Lange |first27=Ethan |last28=LeBoff |first28=Meryl |last29=Lee |first29=Seunggeun |last30=Li |first30=Xihao |last31=Li |first31=Zilin |last32=Lim |first32=Elise |last33=Lin |first33=Danyu |last34=Lin |first34=Xihong |last35=Liu |first35=Simin |last36=Lu |first36=Yingchang |last37=Manson |first37=JoAnn |last38=Martin |first38=Lisa |last39=McHugh |first39=Caitlin |last40=Mikulla |first40=Julie |last41=Musani |first41=Solomon K. |last42=Ng |first42=Maggie |last43=Nickerson |first43=Deborah |last44=Palmer |first44=Nicholette |last45=Perry |first45=James |last46=Peters |first46=Ulrike |last47=Preuss |first47=Michael |last48=Qi |first48=Qibin |last49=Raffield |first49=Laura |last50=Rasmussen-Torvik |first50=Laura |last51=Reiner |first51=Alex |last52=Russell |first52=Emily M. |last53=Sitlani |first53=Colleen |last54=Smith |first54=Jennifer |last55=Spracklen |first55=Cassandra N. |last56=Wang |first56=Tao |last57=Wang |first57=Zhe |last58=Wessel |first58=Jennifer |last59=Xu |first59=Hanfei |last60=Yaser |first60=Mohammad |last61=Yoneyama |first61=Sachiko |last62=Young |first62=Kendra A. |last63=Zhang |first63=Jingwen |last64=Zhang |first64=Xinruo |last65=Zhou |first65=Hufeng |last66=Zhu |first66=Xiaofeng |last67=Zoellner |first67=Sebastian |last68=Abe |first68=Namiko |last69=Abecasis |first69=Gonçalo |last70=Aguet |first70=Francois |last71=Almasy |first71=Laura |last72=Alonso |first72=Alvaro |last73=Ament |first73=Seth |last74=Anderson |first74=Peter |last75=Anugu |first75=Pramod |last76=Applebaum-Bowden |first76=Deborah |last77=Ardlie |first77=Kristin |last78=Arking |first78=Dan |last79=Ashley-Koch |first79=Allison |last80=Assimes |first80=Tim |last81=Auer |first81=Paul |last82=Avramopoulos |first82=Dimitrios |last83=Ayas |first83=Najib |last84=Balasubramanian |first84=Adithya |last85=Barnard |first85=John |last86=Barnes |first86=Kathleen |last87=Barr |first87=R. Graham |last88=Barron-Casella |first88=Emily |last89=Barwick |first89=Lucas |last90=Beaty |first90=Terri |last91=Beck |first91=Gerald |last92=Becker |first92=Lewis |last93=Beer |first93=Rebecca |last94=Beitelshees |first94=Amber |last95=Benjamin |first95=Emelia |last96=Benos |first96=Takis |last97=Bezerra |first97=Marcos |last98=Bielak |first98=Larry |last99=Bis |first99=Joshua |last100=Blackwell |first100=Thomas |last101=Blangero |first101=John |last102=Bowden |first102=Donald W. |last103=Bowler |first103=Russell |last104=Broeckel |first104=Ulrich |last105=Broome |first105=Jai |last106=Brown |first106=Deborah |last107=Bunting |first107=Karen |last108=Burchard |first108=Esteban |last109=Bustamante |first109=Carlos |last110=Buth |first110=Erin |last111=Cade |first111=Brian |last112=Cardwell |first112=Jonathan |last113=Carey |first113=Vincent |last114=Carrier |first114=Julie |last115=Carson |first115=April |last116=Carty |first116=Cara |last117=Casaburi |first117=Richard |last118=Romero |first118=Juan P. Casas |last119=Casella |first119=James |last120=Castaldi |first120=Peter |last121=Chaffin |first121=Mark |last122=Chang |first122=Christy |last123=Chang |first123=Yi-Cheng |last124=Chavan |first124=Sameer |last125=Chen |first125=Bo-Juen |last126=Chen |first126=Wei-Min |last127=Cho |first127=Michael |last128=Choi |first128=Seung Hoan |last129=Chuang |first129=Lee-Ming |last130=Chung |first130=Ren-Hua |last131=Clish |first131=Clary |last132=Comhair |first132=Suzy |last133=Conomos |first133=Matthew |last134=Cornell |first134=Elaine |last135=Crandall |first135=Carolyn |last136=Crapo |first136=James |last137=Curran |first137=Joanne |last138=Curtis |first138=Jeffrey |last139=Custer |first139=Brian |last140=Damcott |first140=Coleen |last141=Darbar |first141=Dawood |last142=David |first142=Sean |last143=Davis |first143=Colleen |last144=Daya |first144=Michelle |last145=de las Fuentes |first145=Lisa |last146=de Vries |first146=Paul |last147=DeBaun |first147=Michael |last148=Deka |first148=Ranjan |last149=DeMeo |first149=Dawn |last150=Devine |first150=Scott |last151=Dinh |first151=Huyen |last152=Doddapaneni |first152=Harsha |last153=Duan |first153=Qing |last154=Dugan-Perez |first154=Shannon |last155=Duggirala |first155=Ravi |last156=Durda |first156=Jon Peter |last157=Dutcher |first157=Susan K. |last158=Eaton |first158=Charles |last159=Ekunwe |first159=Lynette |last160=El Boueiz |first160=Adel |last161=Emery |first161=Leslie |last162=Erzurum |first162=Serpil |last163=Farber |first163=Charles |last164=Farek |first164=Jesse |last165=Fingerlin |first165=Tasha |last166=Flickinger |first166=Matthew |last167=Franceschini |first167=Nora |last168=Frazar |first168=Chris |last169=Fu |first169=Mao |last170=Fullerton |first170=Stephanie M. |last171=Fulton |first171=Lucinda |last172=Gabriel |first172=Stacey |last173=Gan |first173=Weiniu |last174=Gao |first174=Shanshan |last175=Gao |first175=Yan |last176=Gass |first176=Margery |last177=Geiger |first177=Heather |last178=Gelb |first178=Bruce |last179=Geraci |first179=Mark |last180=Germer |first180=Soren |last181=Gerszten |first181=Robert |last182=Ghosh |first182=Auyon |last183=Gibbs |first183=Richard |last184=Gignoux |first184=Chris |last185=Gladwin |first185=Mark |last186=Glahn |first186=David |last187=Gogarten |first187=Stephanie |last188=Gong |first188=Da-Wei |last189=Goring |first189=Harald |last190=Graw |first190=Sharon |last191=Gray |first191=Kathryn J. |last192=Grine |first192=Daniel |last193=Gross |first193=Colin |last194=Gu |first194=C. Charles |last195=Guan |first195=Yue |last196=Gupta |first196=Namrata |last197=Haas |first197=David M. |last198=Haessler |first198=Jeff |last199=Hall |first199=Michael |last200=Han |first200=Yi |last201=Hanly |first201=Patrick |last202=Harris |first202=Daniel |last203=Hawley |first203=Nicola L. |last204=Heavner |first204=Ben |last205=Herrington |first205=David |last206=Hersh |first206=Craig |last207=Hidalgo |first207=Bertha |last208=Hixson |first208=James |last209=Hobbs |first209=Brian |last210=Hokanson |first210=John |last211=Hong |first211=Elliott |last212=Hoth |first212=Karin |last213=Hsiung |first213=Chao Agnes |last214=Hu |first214=Jianhong |last215=Hung |first215=Yi-Jen |last216=Huston |first216=Haley |last217=Hwu |first217=Chii Min |last218=Irvin |first218=Marguerite Ryan |last219=Jaquish |first219=Cashell |last220=Johnsen |first220=Jill |last221=Johnson |first221=Andrew |last222=Johnson |first222=Craig |last223=Johnston |first223=Rich |last224=Jones |first224=Kimberly |last225=Kang |first225=Hyun Min |last226=Kaplan |first226=Robert |last227=Kelly |first227=Shannon |last228=Kenny |first228=Eimear |last229=Kessler |first229=Michael |last230=Khan |first230=Alyna |last231=Khan |first231=Ziad |last232=Kim |first232=Wonji |last233=Kimoff |first233=John |last234=Kinney |first234=Greg |last235=Konkle |first235=Barbara |last236=Kramer |first236=Holly |last237=Lange |first237=Christoph |last238=Lee |first238=Jiwon |last239=Lee |first239=Sandra |last240=Lee |first240=Wen-Jane |last241=LeFaive |first241=Jonathon |last242=Levine |first242=David |last243=Levy |first243=Dan |last244=Lewis |first244=Joshua |last245=Li |first245=Xiaohui |last246=Li |first246=Yun |last247=Lin |first247=Henry |last248=Lin |first248=Honghuang |last249=Liu |first249=Yongmei |last250=Liu |first250=Yu |last251=Lunetta |first251=Kathryn |last252=Luo |first252=James |last253=Magalang |first253=Ulysses |last254=Mahaney |first254=Michael |last255=Make |first255=Barry |last256=Manichaikul |first256=Ani |last257=Manning |first257=Alisa |last258=Marton |first258=Melissa |last259=Mathai |first259=Susan |last260=May |first260=Susanne |last261=McArdle |first261=Patrick |last262=McFarland |first262=Sean |last263=McGoldrick |first263=Daniel |last264=McNeil |first264=Becky |last265=Mei |first265=Hao |last266=Meigs |first266=James |last267=Menon |first267=Vipin |last268=Mestroni |first268=Luisa |last269=Metcalf |first269=Ginger |last270=Meyers |first270=Deborah A. |last271=Mignot |first271=Emmanuel |last272=Mikulla |first272=Julie |last273=Min |first273=Nancy |last274=Minear |first274=Mollie |last275=Minster |first275=Ryan L. |last276=Moll |first276=Matt |last277=Momin |first277=Zeineen |last278=Montasser |first278=May E. |last279=Montgomery |first279=Courtney |last280=Muzny |first280=Donna |last281=Mychaleckyj |first281=Josyf C. |last282=Nadkarni |first282=Girish |last283=Naik |first283=Rakhi |last284=Naseri |first284=Take |last285=Natarajan |first285=Pradeep |last286=Nekhai |first286=Sergei |last287=Nelson |first287=Sarah C. |last288=Neltner |first288=Bonnie |last289=Nessner |first289=Caitlin |last290=Nkechinyere |first290=Osuji |last291=O'Connor |first291=Tim |last292=Ochs-Balcom |first292=Heather |last293=Okwuonu |first293=Geoffrey |last294=Pack |first294=Allan |last295=Paik |first295=David T. |last296=Palmer |first296=Nicholette |last297=Pankow |first297=James |last298=Papanicolaou |first298=George |last299=Parker |first299=Cora |last300=Peloso |first300=Gina |last301=Peralta |first301=Juan Manuel |last302=Perez |first302=Marco |last303=Peyser |first303=Patricia |last304=Phillips |first304=Lawrence S. |last305=Pleiness |first305=Jacob |last306=Pollin |first306=Toni |last307=Post |first307=Wendy |last308=Becker |first308=Julia Powers |last309=Boorgula |first309=Meher Preethi |last310=Qasba |first310=Pankaj |last311=Qiao |first311=Dandi |last312=Qin |first312=Zhaohui |last313=Rafaels |first313=Nicholas |last314=Rajendran |first314=Mahitha |last315=Rao |first315=D. C. |last316=Ratan |first316=Aakrosh |last317=Reed |first317=Robert |last318=Reeves |first318=Catherine |last319=Reupena |first319=Muagututi'a Sefuiva |last320=Rice |first320=Ken |last321=Robillard |first321=Rebecca |last322=Robine |first322=Nicolas |last323=Roselli |first323=Carolina |last324=Ruczinski |first324=Ingo |last325=Runnels |first325=Alexi |last326=Russell |first326=Pamela |last327=Ruuska |first327=Sarah |last328=Ryan |first328=Kathleen |last329=Sabino |first329=Ester Cerdeira |last330=Saleheen |first330=Danish |last331=Salimi |first331=Shabnam |last332=Salvi |first332=Sejal |last333=Salzberg |first333=Steven |last334=Sandow |first334=Kevin |last335=Sankaran |first335=Vijay G. |last336=Santibanez |first336=Jireh |last337=Schwander |first337=Karen |last338=Schwartz |first338=David |last339=Sciurba |first339=Frank |last340=Seidman |first340=Christine |last341=Seidman |first341=Jonathan |last342=Sheehan |first342=Vivien |last343=Sherman |first343=Stephanie L. |last344=Shetty |first344=Amol |last345=Shetty |first345=Aniket |last346=Sheu |first346=Wayne Hui-Heng |last347=Silver |first347=Brian |last348=Silverman |first348=Edwin |last349=Skomro |first349=Robert |last350=Smith |first350=Albert Vernon |last351=Smith |first351=Josh |last352=Smith |first352=Tanja |last353=Smoller |first353=Sylvia |last354=Snively |first354=Beverly |last355=Snyder |first355=Michael |last356=Sofer |first356=Tamar |last357=Sotoodehnia |first357=Nona |last358=Stilp |first358=Adrienne M. |last359=Storm |first359=Garrett |last360=Streeten |first360=Elizabeth |last361=Su |first361=Jessica Lasky |last362=Sung |first362=Yun Ju |last363=Sylvia |first363=Jody |last364=Szpiro |first364=Adam |last365=Taliun |first365=Daniel |last366=Tang |first366=Hua |last367=Taub |first367=Margaret |last368=Taylor |first368=Kent D. |last369=Taylor |first369=Matthew |last370=Taylor |first370=Simeon |last371=Telen |first371=Marilyn |last372=Thornton |first372=Timothy A. |last373=Threlkeld |first373=Machiko |last374=Tinker |first374=Lesley |last375=Tirschwell |first375=David |last376=Tishkoff |first376=Sarah |last377=Tiwari |first377=Hemant |last378=Tong |first378=Catherine |last379=Tracy |first379=Russell |last380=Tsai |first380=Michael |last381=Vaidya |first381=Dhananjay |last382=Van Den Berg |first382=David |last383=VandeHaar |first383=Peter |last384=Vrieze |first384=Scott |last385=Walker |first385=Tarik |last386=Wallace |first386=Robert |last387=Walts |first387=Avram |last388=Wang |first388=Fei Fei |last389=Wang |first389=Heming |last390=Wang |first390=Jiongming |last391=Watson |first391=Karol |last392=Watt |first392=Jennifer |last393=Weeks |first393=Daniel E. |last394=Weinstock |first394=Joshua |last395=Weiss |first395=Scott T. |last396=Weng |first396=Lu-Chen |last397=Willer |first397=Cristen |last398=Williams |first398=Kayleen |last399=Williams |first399=L. Keoki |last400=Wilson |first400=Carla |last401=Wilson |first401=James |last402=Winterkorn |first402=Lara |last403=Wong |first403=Quenna |last404=Wu |first404=Joseph |last405=Xu |first405=Huichun |last406=Yang |first406=Ivana |last407=Yu |first407=Ketian |last408=Zekavat |first408=Seyedeh Maryam |last409=Zhang |first409=Yingze |last410=Zhao |first410=Snow Xueyan |last411=Zhao |first411=Wei |last412=Zody |first412=Michael |last413=Cupples |first413=L. Adrienne |last414=Shadyab |first414=Aladdin H. |last415=McKnight |first415=Barbara |last416=Shoemaker |first416=Benjamin M. |last417=Mitchell |first417=Braxton D. |last418=Psaty |first418=Bruce M. |last419=Kooperberg |first419=Charles |last420=Liu |first420=Ching-Ti |last421=Albert |first421=Christine M. |last422=Roden |first422=Dan |last423=Chasman |first423=Daniel I. |last424=Darbar |first424=Dawood |last425=Lloyd-Jones |first425=Donald M. |last426=Arnett |first426=Donna K. |last427=Regan |first427=Elizabeth A. |last428=Boerwinkle |first428=Eric |last429=Rotter |first429=Jerome I. |last430=O'Connell |first430=Jeffrey R. |last431=Yanek |first431=Lisa R. |last432=de Andrade |first432=Mariza |last433=Allison |first433=Matthew A. |last434=McDonald |first434=Merry-Lynn N. |last435=Chung |first435=Mina K. |last436=Fornage |first436=Myriam |last437=Chami |first437=Nathalie |last438=Smith |first438=Nicholas L. |last439=Ellinor |first439=Patrick T. |last440=Vasan |first440=Ramachandran S. |last441=Mathias |first441=Rasika A. |last442=Loos |first442=Ruth J. F. |last443=Rich |first443=Stephen S. |last444=Lubitz |first444=Steven A. |last445=Heckbert |first445=Susan R. |last446=Redline |first446=Susan |last447=Guo |first447=Xiuqing |last448=Chen |first448=Y. -D Ida |last449=Laurie |first449=Cecelia A. |last450=Hernandez |first450=Ryan D. |last451=McGarvey |first451=Stephen T. |last452=Goddard |first452=Michael E. |last453=Laurie |first453=Cathy C. |last454=North |first454=Kari E. |last455=Lange |first455=Leslie A. |last456=Weir |first456=Bruce S. |last457=Yengo |first457=Loic |last458=Yang |first458=Jian |last459=Visscher |first459=Peter M.|title=Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data |journal=Nature Genetics |date=March 2022 |volume=54 |issue=3 |pages=263–273 |doi=10.1038/s41588-021-00997-7|pmid=35256806 |pmc=9119698 }}</ref> Large-scale [[whole genome sequencing]] studies have rapidly sequenced millions of whole genomes, and such studies have identified hundreds of millions of [[rare functional variant|rare variants]].<ref>{{cite journal |last1=Taliun |first1=Daniel |last2=Harris |first2=Daniel N. |last3=Kessler |first3=Michael D. |last4=Carlson |first4=Jedidiah |last5=Szpiech |first5=Zachary A. |last6=Torres |first6=Raul |last7=Taliun |first7=Sarah A. Gagliano |last8=Corvelo |first8=André |last9=Gogarten |first9=Stephanie M. |last10=Kang |first10=Hyun Min |last11=Pitsillides |first11=Achilleas N. |last12=LeFaive |first12=Jonathon |last13=Lee |first13=Seung-been |last14=Tian |first14=Xiaowen |last15=Browning |first15=Brian L. |last16=Das |first16=Sayantan |last17=Emde |first17=Anne-Katrin |last18=Clarke |first18=Wayne E. |last19=Loesch |first19=Douglas P. |last20=Shetty |first20=Amol C. |last21=Blackwell |first21=Thomas W. |last22=Smith |first22=Albert V. |last23=Wong |first23=Quenna |last24=Liu |first24=Xiaoming |last25=Conomos |first25=Matthew P. |last26=Bobo |first26=Dean M. |last27=Aguet |first27=François |last28=Albert |first28=Christine |last29=Alonso |first29=Alvaro |last30=Ardlie |first30=Kristin G. |last31=Arking |first31=Dan E. |last32=Aslibekyan |first32=Stella |last33=Auer |first33=Paul L. |last34=Barnard |first34=John |last35=Barr |first35=R. Graham |last36=Barwick |first36=Lucas |last37=Becker |first37=Lewis C. |last38=Beer |first38=Rebecca L. |last39=Benjamin |first39=Emelia J. |last40=Bielak |first40=Lawrence F. |last41=Blangero |first41=John |last42=Boehnke |first42=Michael |last43=Bowden |first43=Donald W. |last44=Brody |first44=Jennifer A. |last45=Burchard |first45=Esteban G. |last46=Cade |first46=Brian E. |last47=Casella |first47=James F. |last48=Chalazan |first48=Brandon |last49=Chasman |first49=Daniel I. |last50=Chen |first50=Yii-Der Ida |last51=Cho |first51=Michael H. |last52=Choi |first52=Seung Hoan |last53=Chung |first53=Mina K. |last54=Clish |first54=Clary B. |last55=Correa |first55=Adolfo |last56=Curran |first56=Joanne E. |last57=Custer |first57=Brian |last58=Darbar |first58=Dawood |last59=Daya |first59=Michelle |last60=de Andrade |first60=Mariza |last61=DeMeo |first61=Dawn L. |last62=Dutcher |first62=Susan K. |last63=Ellinor |first63=Patrick T. |last64=Emery |first64=Leslie S. |last65=Eng |first65=Celeste |last66=Fatkin |first66=Diane |last67=Fingerlin |first67=Tasha |last68=Forer |first68=Lukas |last69=Fornage |first69=Myriam |last70=Franceschini |first70=Nora |last71=Fuchsberger |first71=Christian |last72=Fullerton |first72=Stephanie M. |last73=Germer |first73=Soren |last74=Gladwin |first74=Mark T. |last75=Gottlieb |first75=Daniel J. |last76=Guo |first76=Xiuqing |last77=Hall |first77=Michael E. |last78=He |first78=Jiang |last79=Heard-Costa |first79=Nancy L. |last80=Heckbert |first80=Susan R. |last81=Irvin |first81=Marguerite R. |last82=Johnsen |first82=Jill M. |last83=Johnson |first83=Andrew D. |last84=Kaplan |first84=Robert |last85=Kardia |first85=Sharon L. R. |last86=Kelly |first86=Tanika |last87=Kelly |first87=Shannon |last88=Kenny |first88=Eimear E. |last89=Kiel |first89=Douglas P. |last90=Klemmer |first90=Robert |last91=Konkle |first91=Barbara A. |last92=Kooperberg |first92=Charles |last93=Köttgen |first93=Anna |last94=Lange |first94=Leslie A. |last95=Lasky-Su |first95=Jessica |last96=Levy |first96=Daniel |last97=Lin |first97=Xihong |last98=Lin |first98=Keng-Han |last99=Liu |first99=Chunyu |display-authors=1 |last100=Loos |first100=Ruth J. F. |last101=Garman |first101=Lori |last102=Gerszten |first102=Robert |last103=Lubitz |first103=Steven A. |last104=Lunetta |first104=Kathryn L. |last105=Mak |first105=Angel C. Y. |last106=Manichaikul |first106=Ani |last107=Manning |first107=Alisa K. |last108=Mathias |first108=Rasika A. |last109=McManus |first109=David D. |last110=McGarvey |first110=Stephen T. |last111=Meigs |first111=James B. |last112=Meyers |first112=Deborah A. |last113=Mikulla |first113=Julie L. |last114=Minear |first114=Mollie A. |last115=Mitchell |first115=Braxton D. |last116=Mohanty |first116=Sanghamitra |last117=Montasser |first117=May E. |last118=Montgomery |first118=Courtney |last119=Morrison |first119=Alanna C. |last120=Murabito |first120=Joanne M. |last121=Natale |first121=Andrea |last122=Natarajan |first122=Pradeep |last123=Nelson |first123=Sarah C. |last124=North |first124=Kari E. |last125=O'Connell |first125=Jeffrey R. |last126=Palmer |first126=Nicholette D. |last127=Pankratz |first127=Nathan |last128=Peloso |first128=Gina M. |last129=Peyser |first129=Patricia A. |last130=Pleiness |first130=Jacob |last131=Post |first131=Wendy S. |last132=Psaty |first132=Bruce M. |last133=Rao |first133=D. C. |last134=Redline |first134=Susan |last135=Reiner |first135=Alexander P. |last136=Roden |first136=Dan |last137=Rotter |first137=Jerome I. |last138=Ruczinski |first138=Ingo |last139=Sarnowski |first139=Chloé |last140=Schoenherr |first140=Sebastian |last141=Schwartz |first141=David A. |last142=Seo |first142=Jeong-Sun |last143=Seshadri |first143=Sudha |last144=Sheehan |first144=Vivien A. |last145=Sheu |first145=Wayne H. |last146=Shoemaker |first146=M. Benjamin |last147=Smith |first147=Nicholas L. |last148=Smith |first148=Jennifer A. |last149=Sotoodehnia |first149=Nona |last150=Stilp |first150=Adrienne M. |last151=Tang |first151=Weihong |last152=Taylor |first152=Kent D. |last153=Telen |first153=Marilyn |last154=Thornton |first154=Timothy A. |last155=Tracy |first155=Russell P. |last156=Van Den Berg |first156=David J. |last157=Vasan |first157=Ramachandran S. |last158=Viaud-Martinez |first158=Karine A. |last159=Vrieze |first159=Scott |last160=Weeks |first160=Daniel E. |last161=Weir |first161=Bruce S. |last162=Weiss |first162=Scott T. |last163=Weng |first163=Lu-Chen |last164=Willer |first164=Cristen J. |last165=Zhang |first165=Yingze |last166=Zhao |first166=Xutong |last167=Arnett |first167=Donna K. |last168=Ashley-Koch |first168=Allison E. |last169=Barnes |first169=Kathleen C. |last170=Boerwinkle |first170=Eric |last171=Gabriel |first171=Stacey |last172=Gibbs |first172=Richard |last173=Rice |first173=Kenneth M. |last174=Rich |first174=Stephen S. |last175=Silverman |first175=Edwin K. |last176=Qasba |first176=Pankaj |last177=Gan |first177=Weiniu |last178=Papanicolaou |first178=George J. |last179=Nickerson |first179=Deborah A. |last180=Browning |first180=Sharon R. |last181=Zody |first181=Michael C. |last182=Zöllner |first182=Sebastian |last183=Wilson |first183=James G. |last184=Cupples |first184=L. Adrienne |last185=Laurie |first185=Cathy C. |last186=Jaquish |first186=Cashell E. |last187=Hernandez |first187=Ryan D. |last188=O'Connor |first188=Timothy D. |last189=Abecasis |first189=Gonçalo R. |title=Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program |journal=Nature |date=February 2021 |volume=590 |issue=7845 |pages=290–299 |doi=10.1038/s41586-021-03205-y|pmid=33568819 |pmc=7875770 |bibcode=2021Natur.590..290T }}</ref> [[SNP annotation|Functional annotations]] predict the effect or function of a genetic variant and help to prioritize rare functional variants, and incorporating these annotations can effectively boost the power of genetic association of rare variants analysis of whole genome sequencing studies.<ref>{{cite journal |last1=Li |first1=Xihao |last2=Li |first2=Zilin |last3=Zhou |first3=Hufeng |last4=Gaynor |first4=Sheila M. |last5=Liu |first5=Yaowu |last6=Chen |first6=Han |last7=Sun |first7=Ryan |last8=Dey |first8=Rounak |last9=Arnett |first9=Donna K. |last10=Aslibekyan |first10=Stella |last11=Ballantyne |first11=Christie M. |last12=Bielak |first12=Lawrence F. |last13=Blangero |first13=John |last14=Boerwinkle |first14=Eric |last15=Bowden |first15=Donald W. |last16=Broome |first16=Jai G. |last17=Conomos |first17=Matthew P. |last18=Correa |first18=Adolfo |last19=Cupples |first19=L. Adrienne |last20=Curran |first20=Joanne E. |last21=Freedman |first21=Barry I. |last22=Guo |first22=Xiuqing |last23=Hindy |first23=George |last24=Irvin |first24=Marguerite R. |last25=Kardia |first25=Sharon L. R. |last26=Kathiresan |first26=Sekar |last27=Khan |first27=Alyna T. |last28=Kooperberg |first28=Charles L. |last29=Laurie |first29=Cathy C. |last30=Liu |first30=X. Shirley |last31=Mahaney |first31=Michael C. |last32=Manichaikul |first32=Ani W. |last33=Martin |first33=Lisa W. |last34=Mathias |first34=Rasika A. |last35=McGarvey |first35=Stephen T. |last36=Mitchell |first36=Braxton D. |last37=Montasser |first37=May E. |last38=Moore |first38=Jill E. |last39=Morrison |first39=Alanna C. |last40=O'Connell |first40=Jeffrey R. |last41=Palmer |first41=Nicholette D. |last42=Pampana |first42=Akhil |last43=Peralta |first43=Juan M. |last44=Peyser |first44=Patricia A. |last45=Psaty |first45=Bruce M. |last46=Redline |first46=Susan |last47=Rice |first47=Kenneth M. |last48=Rich |first48=Stephen S. |last49=Smith |first49=Jennifer A. |last50=Tiwari |first50=Hemant K. |last51=Tsai |first51=Michael Y. |last52=Vasan |first52=Ramachandran S. |last53=Wang |first53=Fei Fei |last54=Weeks |first54=Daniel E. |last55=Weng |first55=Zhiping |last56=Wilson |first56=James G. |last57=Yanek |first57=Lisa R. |last58=Abe |first58=Namiko |last59=Abecasis |first59=Gonçalo R. |last60=Aguet |first60=Francois |last61=Albert |first61=Christine |last62=Almasy |first62=Laura |last63=Alonso |first63=Alvaro |last64=Ament |first64=Seth |last65=Anderson |first65=Peter |last66=Anugu |first66=Pramod |last67=Applebaum-Bowden |first67=Deborah |last68=Ardlie |first68=Kristin |last69=Arking |first69=Dan |last70=Arnett |first70=Donna K. |last71=Ashley-Koch |first71=Allison |last72=Aslibekyan |first72=Stella |last73=Assimes |first73=Tim |last74=Auer |first74=Paul |last75=Avramopoulos |first75=Dimitrios |last76=Barnard |first76=John |last77=Barnes |first77=Kathleen |last78=Barr |first78=R. Graham |last79=Barron-Casella |first79=Emily |last80=Barwick |first80=Lucas |last81=Beaty |first81=Terri |last82=Beck |first82=Gerald |last83=Becker |first83=Diane |last84=Becker |first84=Lewis |last85=Beer |first85=Rebecca |last86=Beitelshees |first86=Amber |last87=Benjamin |first87=Emelia |last88=Benos |first88=Takis |last89=Bezerra |first89=Marcos |last90=Bielak |first90=Lawrence F. |last91=Bis |first91=Joshua |last92=Blackwell |first92=Thomas |last93=Blangero |first93=John |last94=Boerwinkle |first94=Eric |last95=Bowden |first95=Donald W. |last96=Bowler |first96=Russell |last97=Brody |first97=Jennifer |last98=Broeckel |first98=Ulrich |last99=Broome |first99=Jai G. |last100=Bunting |first100=Karen |last101=Burchard |first101=Esteban |last102=Bustamante |first102=Carlos |last103=Buth |first103=Erin |last104=Cade |first104=Brian |last105=Cardwell |first105=Jonathan |last106=Carey |first106=Vincent |last107=Carty |first107=Cara |last108=Casaburi |first108=Richard |last109=Casella |first109=James |last110=Castaldi |first110=Peter |last111=Chaffin |first111=Mark |last112=Chang |first112=Christy |last113=Chang |first113=Yi-Cheng |last114=Chasman |first114=Daniel |last115=Chavan |first115=Sameer |last116=Chen |first116=Bo-Juen |last117=Chen |first117=Wei-Min |last118=Chen |first118=Yii-Der Ida |last119=Cho |first119=Michael |last120=Choi |first120=Seung Hoan |last121=Chuang |first121=Lee-Ming |last122=Chung |first122=Mina |last123=Chung |first123=Ren-Hua |last124=Clish |first124=Clary |last125=Comhair |first125=Suzy |last126=Conomos |first126=Matthew P. |last127=Cornell |first127=Elaine |last128=Correa |first128=Adolfo |last129=Crandall |first129=Carolyn |last130=Crapo |first130=James |last131=Cupples |first131=L. Adrienne |last132=Curran |first132=Joanne E. |last133=Curtis |first133=Jeffrey |last134=Custer |first134=Brian |last135=Damcott |first135=Coleen |last136=Darbar |first136=Dawood |last137=Das |first137=Sayantan |last138=David |first138=Sean |last139=Davis |first139=Colleen |last140=Daya |first140=Michelle |last141=de Andrade |first141=Mariza |last142=Fuentes |first142=Lisa de las |last143=DeBaun |first143=Michael |last144=Deka |first144=Ranjan |last145=DeMeo |first145=Dawn |last146=Devine |first146=Scott |last147=Duan |first147=Qing |last148=Duggirala |first148=Ravi |last149=Durda |first149=Jon Peter |last150=Dutcher |first150=Susan |last151=Eaton |first151=Charles |last152=Ekunwe |first152=Lynette |last153=El Boueiz |first153=Adel |last154=Ellinor |first154=Patrick |last155=Emery |first155=Leslie |last156=Erzurum |first156=Serpil |last157=Farber |first157=Charles |last158=Fingerlin |first158=Tasha |last159=Flickinger |first159=Matthew |last160=Fornage |first160=Myriam |last161=Franceschini |first161=Nora |last162=Frazar |first162=Chris |last163=Fu |first163=Mao |last164=Fullerton |first164=Stephanie M. |last165=Fulton |first165=Lucinda |last166=Gabriel |first166=Stacey |last167=Gan |first167=Weiniu |last168=Gao |first168=Shanshan |last169=Gao |first169=Yan |last170=Gass |first170=Margery |last171=Gelb |first171=Bruce |last172=Geng |first172=Xiaoqi |last173=Geraci |first173=Mark |last174=Germer |first174=Soren |last175=Gerszten |first175=Robert |last176=Ghosh |first176=Auyon |last177=Gibbs |first177=Richard |last178=Gignoux |first178=Chris |last179=Gladwin |first179=Mark |last180=Glahn |first180=David |last181=Gogarten |first181=Stephanie |last182=Gong |first182=Da-Wei |last183=Goring |first183=Harald |last184=Graw |first184=Sharon |last185=Grine |first185=Daniel |last186=Gu |first186=C. Charles |last187=Guan |first187=Yue |last188=Guo |first188=Xiuqing |last189=Gupta |first189=Namrata |last190=Haessler |first190=Jeff |last191=Hall |first191=Michael |last192=Harris |first192=Daniel |last193=Hawley |first193=Nicola L. |last194=He |first194=Jiang |last195=Heckbert |first195=Susan |last196=Hernandez |first196=Ryan |last197=Herrington |first197=David |last198=Hersh |first198=Craig |last199=Hidalgo |first199=Bertha |last200=Hixson |first200=James |last201=Hobbs |first201=Brian |last202=Hokanson |first202=John |last203=Hong |first203=Elliott |last204=Hoth |first204=Karin |last205=Hsiung |first205=Chao |last206=Hung |first206=Yi-Jen |last207=Huston |first207=Haley |last208=Hwu |first208=Chii Min |last209=Irvin |first209=Marguerite R. |last210=Jackson |first210=Rebecca |last211=Jain |first211=Deepti |last212=Jaquish |first212=Cashell |last213=Jhun |first213=Min A. |last214=Johnsen |first214=Jill |last215=Johnson |first215=Andrew |last216=Johnson |first216=Craig |last217=Johnston |first217=Rich |last218=Jones |first218=Kimberly |last219=Kang |first219=Hyun Min |last220=Kaplan |first220=Robert |last221=Kardia |first221=Sharon L. R. |last222=Kathiresan |first222=Sekar |last223=Kelly |first223=Shannon |last224=Kenny |first224=Eimear |last225=Kessler |first225=Michael |last226=Khan |first226=Alyna T. |last227=Kim |first227=Wonji |last228=Kinney |first228=Greg |last229=Konkle |first229=Barbara |last230=Kooperberg |first230=Charles L. |last231=Kramer |first231=Holly |last232=Lange |first232=Christoph |last233=Lange |first233=Ethan |last234=Lange |first234=Leslie |last235=Laurie |first235=Cathy C. |last236=Laurie |first236=Cecelia |last237=LeBoff |first237=Meryl |last238=Lee |first238=Jiwon |last239=Lee |first239=Seunggeun Shawn |last240=Lee |first240=Wen-Jane |last241=LeFaive |first241=Jonathon |last242=Levine |first242=David |last243=Levy |first243=Dan |last244=Lewis |first244=Joshua |last245=Li |first245=Xiaohui |last246=Li |first246=Yun |last247=Lin |first247=Henry |last248=Lin |first248=Honghuang |last249=Lin |first249=Keng Han |last250=Lin |first250=Xihong |last251=Liu |first251=Simin |last252=Liu |first252=Yongmei |last253=Liu |first253=Yu |last254=Loos |first254=Ruth J. F. |last255=Lubitz |first255=Steven |last256=Lunetta |first256=Kathryn |last257=Luo |first257=James |last258=Mahaney |first258=Michael C. |last259=Make |first259=Barry |last260=Manichaikul |first260=Ani W. |last261=Manson |first261=JoAnn |last262=Margolin |first262=Lauren |last263=Martin |first263=Lisa W. |last264=Mathai |first264=Susan |last265=Mathias |first265=Rasika A. |last266=May |first266=Susanne |last267=McArdle |first267=Patrick |last268=McDonald |first268=Merry-Lynn |last269=McFarland |first269=Sean |last270=McGarvey |first270=Stephen T. |last271=McGoldrick |first271=Daniel |last272=McHugh |first272=Caitlin |last273=Mei |first273=Hao |last274=Mestroni |first274=Luisa |last275=Meyers |first275=Deborah A. |last276=Mikulla |first276=Julie |last277=Min |first277=Nancy |last278=Minear |first278=Mollie |last279=Minster |first279=Ryan L. |last280=Mitchell |first280=Braxton D. |last281=Moll |first281=Matt |last282=Montasser |first282=May E. |last283=Montgomery |first283=Courtney |last284=Moscati |first284=Arden |last285=Musani |first285=Solomon |last286=Mwasongwe |first286=Stanford |last287=Mychaleckyj |first287=Josyf C. |last288=Nadkarni |first288=Girish |last289=Naik |first289=Rakhi |last290=Naseri |first290=Take |last291=Natarajan |first291=Pradeep |last292=Nekhai |first292=Sergei |last293=Nelson |first293=Sarah C. |last294=Neltner |first294=Bonnie |last295=Nickerson |first295=Deborah |last296=North |first296=Kari |last297=O'Connell |first297=Jeffrey R. |last298=O'Connor |first298=Tim |last299=Ochs-Balcom |first299=Heather |last300=Paik |first300=David |last301=Palmer |first301=Nicholette D. |last302=Pankow |first302=James |last303=Papanicolaou |first303=George |last304=Parsa |first304=Afshin |last305=Peralta |first305=Juan M. |last306=Perez |first306=Marco |last307=Perry |first307=James |last308=Peters |first308=Ulrike |last309=Peyser |first309=Patricia A. |last310=Phillips |first310=Lawrence S. |last311=Pollin |first311=Toni |last312=Post |first312=Wendy |last313=Becker |first313=Julia Powers |last314=Boorgula |first314=Meher Preethi |last315=Preuss |first315=Michael |last316=Psaty |first316=Bruce M. |last317=Qasba |first317=Pankaj |last318=Qiao |first318=Dandi |last319=Qin |first319=Zhaohui |last320=Rafaels |first320=Nicholas |last321=Raffield |first321=Laura |last322=Vasan |first322=Ramachandran S. |last323=Rao |first323=D. C. |last324=Rasmussen-Torvik |first324=Laura |last325=Ratan |first325=Aakrosh |last326=Redline |first326=Susan |last327=Reed |first327=Robert |last328=Regan |first328=Elizabeth |last329=Reiner |first329=Alex |last330=Reupena |first330=Muagututi'a Sefuiva |last331=Rice |first331=Kenneth M. |last332=Rich |first332=Stephen S. |last333=Roden |first333=Dan |last334=Roselli |first334=Carolina |last335=Rotter |first335=Jerome I. |last336=Ruczinski |first336=Ingo |last337=Russell |first337=Pamela |last338=Ruuska |first338=Sarah |last339=Ryan |first339=Kathleen |last340=Sabino |first340=Ester Cerdeira |last341=Saleheen |first341=Danish |last342=Salimi |first342=Shabnam |last343=Salzberg |first343=Steven |last344=Sandow |first344=Kevin |last345=Sankaran |first345=Vijay G. |last346=Scheller |first346=Christopher |last347=Schmidt |first347=Ellen |last348=Schwander |first348=Karen |last349=Schwartz |first349=David |last350=Sciurba |first350=Frank |last351=Seidman |first351=Christine |last352=Seidman |first352=Jonathan |last353=Sheehan |first353=Vivien |last354=Sherman |first354=Stephanie L. |last355=Shetty |first355=Amol |last356=Shetty |first356=Aniket |last357=Sheu |first357=Wayne Hui-Heng |last358=Shoemaker |first358=M. Benjamin |last359=Silver |first359=Brian |last360=Silverman |first360=Edwin |last361=Smith |first361=Jennifer A. |last362=Smith |first362=Josh |last363=Smith |first363=Nicholas |last364=Smith |first364=Tanja |last365=Smoller |first365=Sylvia |last366=Snively |first366=Beverly |last367=Snyder |first367=Michael |last368=Sofer |first368=Tamar |last369=Sotoodehnia |first369=Nona |last370=Stilp |first370=Adrienne M. |last371=Storm |first371=Garrett |last372=Streeten |first372=Elizabeth |last373=Su |first373=Jessica Lasky |last374=Sung |first374=Yun Ju |last375=Sylvia |first375=Jody |last376=Szpiro |first376=Adam |last377=Sztalryd |first377=Carole |last378=Taliun |first378=Daniel |last379=Tang |first379=Hua |last380=Taub |first380=Margaret |last381=Taylor |first381=Kent D. |last382=Taylor |first382=Matthew |last383=Taylor |first383=Simeon |last384=Telen |first384=Marilyn |last385=Thornton |first385=Timothy A. |last386=Threlkeld |first386=Machiko |last387=Tinker |first387=Lesley |last388=Tirschwell |first388=David |last389=Tishkoff |first389=Sarah |last390=Tiwari |first390=Hemant K. |last391=Tong |first391=Catherine |last392=Tracy |first392=Russell |last393=Tsai |first393=Michael Y. |last394=Vaidya |first394=Dhananjay |last395=Van Den Berg |first395=David |last396=VandeHaar |first396=Peter |last397=Vrieze |first397=Scott |last398=Walker |first398=Tarik |last399=Wallace |first399=Robert |last400=Walts |first400=Avram |last401=Wang |first401=Fei Fei |last402=Wang |first402=Heming |last403=Watson |first403=Karol |last404=Weeks |first404=Daniel E. |last405=Weir |first405=Bruce |last406=Weiss |first406=Scott |last407=Weng |first407=Lu-Chen |last408=Wessel |first408=Jennifer |last409=Willer |first409=Cristen J. |last410=Williams |first410=Kayleen |last411=Williams |first411=L. Keoki |last412=Wilson |first412=Carla |last413=Wilson |first413=James G. |last414=Wong |first414=Quenna |last415=Wu |first415=Joseph |last416=Xu |first416=Huichun |last417=Yanek |first417=Lisa R. |last418=Yang |first418=Ivana |last419=Yang |first419=Rongze |last420=Zaghloul |first420=Norann |last421=Zekavat |first421=Maryam |last422=Zhang |first422=Yingze |last423=Zhao |first423=Snow Xueyan |last424=Zhao |first424=Wei |last425=Zhi |first425=Degui |last426=Zhou |first426=Xiang |last427=Zhu |first427=Xiaofeng |last428=Zody |first428=Michael |last429=Zoellner |first429=Sebastian |last430=Abdalla |first430=Moustafa |last431=Abecasis |first431=Gonçalo R. |last432=Arnett |first432=Donna K. |last433=Aslibekyan |first433=Stella |last434=Assimes |first434=Tim |last435=Atkinson |first435=Elizabeth |last436=Ballantyne |first436=Christie M. |last437=Beitelshees |first437=Amber |last438=Bielak |first438=Lawrence F. |last439=Bis |first439=Joshua |last440=Bodea |first440=Corneliu |last441=Boerwinkle |first441=Eric |last442=Bowden |first442=Donald W. |last443=Brody |first443=Jennifer |last444=Cade |first444=Brian |last445=Carlson |first445=Jenna |last446=Chang |first446=I-Shou |last447=Chen |first447=Yii-Der Ida |last448=Chun |first448=Sung |last449=Chung |first449=Ren-Hua |last450=Conomos |first450=Matthew P. |last451=Correa |first451=Adolfo |last452=Cupples |first452=L. Adrienne |last453=Damcott |first453=Coleen |last454=de Vries |first454=Paul |last455=Do |first455=Ron |last456=Elliott |first456=Amanda |last457=Fu |first457=Mao |last458=Ganna |first458=Andrea |last459=Gong |first459=Da-Wei |last460=Graham |first460=Sarah |last461=Haas |first461=Mary |last462=Haring |first462=Bernhard |last463=He |first463=Jiang |last464=Heckbert |first464=Susan |last465=Himes |first465=Blanca |last466=Hixson |first466=James |last467=Irvin |first467=Marguerite R. |last468=Jain |first468=Deepti |last469=Jarvik |first469=Gail |last470=Jhun |first470=Min A. |last471=Jiang |first471=Jicai |last472=Jun |first472=Goo |last473=Kalyani |first473=Rita |last474=Kardia |first474=Sharon L. R. |last475=Kathiresan |first475=Sekar |last476=Khera |first476=Amit |last477=Klarin |first477=Derek |last478=Kooperberg |first478=Charles L. |last479=Kral |first479=Brian |last480=Lange |first480=Leslie |last481=Laurie |first481=Cathy C. |last482=Laurie |first482=Cecelia |last483=Lemaitre |first483=Rozenn |last484=Li |first484=Zilin |last485=Li |first485=Xihao |last486=Lin |first486=Xihong |last487=Mahaney |first487=Michael C. |last488=Manichaikul |first488=Ani W. |last489=Martin |first489=Lisa W. |last490=Mathias |first490=Rasika A. |last491=Mathur |first491=Ravi |last492=McGarvey |first492=Stephen T. |last493=McHugh |first493=Caitlin |last494=McLenithan |first494=John |last495=Mikulla |first495=Julie |last496=Mitchell |first496=Braxton D. |last497=Montasser |first497=May E. |last498=Moran |first498=Andrew |last499=Morrison |first499=Alanna C. |last500=Nakao |first500=Tetsushi |last501=Natarajan |first501=Pradeep |last502=Nickerson |first502=Deborah |last503=North |first503=Kari |last504=O'Connell |first504=Jeffrey R. |last505=O'Donnell |first505=Christopher |last506=Palmer |first506=Nicholette D. |last507=Pampana |first507=Akhil |last508=Patel |first508=Aniruddh |last509=Peloso |first509=Gina M. |last510=Perry |first510=James |last511=Peters |first511=Ulrike |last512=Peyser |first512=Patricia A. |last513=Pirruccello |first513=James |last514=Pollin |first514=Toni |last515=Preuss |first515=Michael |last516=Psaty |first516=Bruce M. |last517=Rao |first517=D. C. |last518=Redline |first518=Susan |last519=Reed |first519=Robert |last520=Reiner |first520=Alex |last521=Rich |first521=Stephen S. |last522=Rosenthal |first522=Samantha |last523=Rotter |first523=Jerome I. |last524=Schoenberg |first524=Jenny |last525=Selvaraj |first525=Margaret Sunitha |last526=Sheu |first526=Wayne Hui-Heng |last527=Smith |first527=Jennifer A. |last528=Sofer |first528=Tamar |last529=Stilp |first529=Adrienne M. |last530=Sunyaev |first530=Shamil R. |last531=Surakka |first531=Ida |last532=Sztalryd |first532=Carole |last533=Tang |first533=Hua |last534=Taylor |first534=Kent D. |last535=Tsai |first535=Michael Y. |last536=Uddin |first536=Md Mesbah |last537=Urbut |first537=Sarah |last538=Verbanck |first538=Marie |last539=Von Holle |first539=Ann |last540=Wang |first540=Heming |last541=Wang |first541=Fei Fei |last542=Wiggins |first542=Kerri |last543=Willer |first543=Cristen J. |last544=Wilson |first544=James G. |last545=Wolford |first545=Brooke |last546=Xu |first546=Huichun |last547=Yanek |first547=Lisa R. |last548=Zaghloul |first548=Norann |last549=Zekavat |first549=Maryam |last550=Zhang |first550=Jingwen |last551=Neale |first551=Benjamin M. |last552=Sunyaev |first552=Shamil R. |last553=Abecasis |first553=Gonçalo R. |last554=Rotter |first554=Jerome I. |last555=Willer |first555=Cristen J. |last556=Peloso |first556=Gina M. |last557=Natarajan |first557=Pradeep |last558=Lin |first558=Xihong|title=Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale |journal=Nature Genetics |date=September 2020 |volume=52 |issue=9 |pages=969–983 |doi=10.1038/s41588-020-0676-4|pmid=32839606 |pmc=7483769 }}</ref> Some tools have been developed to provide all-in-one rare variant association analysis for whole-genome sequencing data, including integration of genotype data and their functional annotations, association analysis, result summary and visualization.<ref>{{cite journal |last1=Li |first1=Zilin |last2=Li |first2=Xihao |last3=Zhou |first3=Hufeng |last4=Gaynor |first4=Sheila M. |last5=Selvaraj |first5=Margaret Sunitha |last6=Arapoglou |first6=Theodore |last7=Quick |first7=Corbin |last8=Liu |first8=Yaowu |last9=Chen |first9=Han |last10=Sun |first10=Ryan |last11=Dey |first11=Rounak |last12=Arnett |first12=Donna K. |last13=Auer |first13=Paul L. |last14=Bielak |first14=Lawrence F. |last15=Bis |first15=Joshua C. |last16=Blackwell |first16=Thomas W. |last17=Blangero |first17=John |last18=Boerwinkle |first18=Eric |last19=Bowden |first19=Donald W. |last20=Brody |first20=Jennifer A. |last21=Cade |first21=Brian E. |last22=Conomos |first22=Matthew P. |last23=Correa |first23=Adolfo |last24=Cupples |first24=L. Adrienne |last25=Curran |first25=Joanne E. |last26=de Vries |first26=Paul S. |last27=Duggirala |first27=Ravindranath |last28=Franceschini |first28=Nora |last29=Freedman |first29=Barry I. |last30=Göring |first30=Harald H. H. |last31=Guo |first31=Xiuqing |last32=Kalyani |first32=Rita R. |last33=Kooperberg |first33=Charles |last34=Kral |first34=Brian G. |last35=Lange |first35=Leslie A. |last36=Lin |first36=Bridget M. |last37=Manichaikul |first37=Ani |last38=Manning |first38=Alisa K. |last39=Martin |first39=Lisa W. |last40=Mathias |first40=Rasika A. |last41=Meigs |first41=James B. |last42=Mitchell |first42=Braxton D. |last43=Montasser |first43=May E. |last44=Morrison |first44=Alanna C. |last45=Naseri |first45=Take |last46=O'Connell |first46=Jeffrey R. |last47=Palmer |first47=Nicholette D. |last48=Peyser |first48=Patricia A. |last49=Psaty |first49=Bruce M. |last50=Raffield |first50=Laura M. |last51=Redline |first51=Susan |last52=Reiner |first52=Alexander P. |last53=Reupena |first53=Muagututi'a Sefuiva |last54=Rice |first54=Kenneth M. |last55=Rich |first55=Stephen S. |last56=Smith |first56=Jennifer A. |last57=Taylor |first57=Kent D. |last58=Taub |first58=Margaret A. |last59=Vasan |first59=Ramachandran S. |last60=Weeks |first60=Daniel E. |last61=Wilson |first61=James G. |last62=Yanek |first62=Lisa R. |last63=Zhao |first63=Wei |last64=Abe |first64=Namiko |last65=Abecasis |first65=Gonçalo |last66=Aguet |first66=Francois |last67=Albert |first67=Christine |last68=Almasy |first68=Laura |last69=Alonso |first69=Alvaro |last70=Ament |first70=Seth |last71=Anderson |first71=Peter |last72=Anugu |first72=Pramod |last73=Applebaum-Bowden |first73=Deborah |last74=Ardlie |first74=Kristin |last75=Arking |first75=Dan |last76=Ashley-Koch |first76=Allison |last77=Aslibekyan |first77=Stella |last78=Assimes |first78=Tim |last79=Avramopoulos |first79=Dimitrios |last80=Ayas |first80=Najib |last81=Balasubramanian |first81=Adithya |last82=Barnard |first82=John |last83=Barnes |first83=Kathleen |last84=Barr |first84=R. Graham |last85=Barron-Casella |first85=Emily |last86=Barwick |first86=Lucas |last87=Beaty |first87=Terri |last88=Beck |first88=Gerald |last89=Becker |first89=Diane |last90=Becker |first90=Lewis |last91=Beer |first91=Rebecca |last92=Beitelshees |first92=Amber |last93=Benjamin |first93=Emelia |last94=Benos |first94=Takis |last95=Bezerra |first95=Marcos |last96=Blue |first96=Nathan |last97=Bowler |first97=Russell |last98=Broeckel |first98=Ulrich |last99=Broome |first99=Jai |last100=Brown |first100=Deborah |last101=Bunting |first101=Karen |last102=Burchard |first102=Esteban |last103=Bustamante |first103=Carlos |last104=Buth |first104=Erin |last105=Cardwell |first105=Jonathan |last106=Carey |first106=Vincent |last107=Carrier |first107=Julie |last108=Carson |first108=April |last109=Carty |first109=Cara |last110=Casaburi |first110=Richard |last111=Casas Romero |first111=Juan P. |last112=Casella |first112=James |last113=Castaldi |first113=Peter |last114=Chaffin |first114=Mark |last115=Chang |first115=Christy |last116=Chang |first116=Yi-Cheng |last117=Chasman |first117=Daniel |last118=Chavan |first118=Sameer |last119=Chen |first119=Bo-Juen |last120=Chen |first120=Wei-Min |last121=Chen |first121=Yii-Der Ida |last122=Cho |first122=Michael |last123=Choi |first123=Seung Hoan |last124=Chuang |first124=Lee-Ming |last125=Chung |first125=Mina |last126=Chung |first126=Ren-Hua |last127=Clish |first127=Clary |last128=Comhair |first128=Suzy |last129=Cornell |first129=Elaine |last130=Crandall |first130=Carolyn |last131=Crapo |first131=James |last132=Curtis |first132=Jeffrey |last133=Custer |first133=Brian |last134=Damcott |first134=Coleen |last135=Darbar |first135=Dawood |last136=David |first136=Sean |last137=Davis |first137=Colleen |last138=Daya |first138=Michelle |last139=de Andrade |first139=Mariza |last140=Fuentes |first140=Lisa de las |last141=DeBaun |first141=Michael |last142=Deka |first142=Ranjan |last143=DeMeo |first143=Dawn |last144=Devine |first144=Scott |last145=Dinh |first145=Huyen |last146=Doddapaneni |first146=Harsha |last147=Duan |first147=Qing |last148=Dugan-Perez |first148=Shannon |last149=Durda |first149=Jon Peter |last150=Dutcher |first150=Susan K. |last151=Eaton |first151=Charles |last152=Ekunwe |first152=Lynette |last153=El Boueiz |first153=Adel |last154=Ellinor |first154=Patrick |last155=Emery |first155=Leslie |last156=Erzurum |first156=Serpil |last157=Farber |first157=Charles |last158=Farek |first158=Jesse |last159=Fingerlin |first159=Tasha |last160=Flickinger |first160=Matthew |last161=Fornage |first161=Myriam |last162=Frazar |first162=Chris |last163=Fu |first163=Mao |last164=Fullerton |first164=Stephanie M. |last165=Fulton |first165=Lucinda |last166=Gabriel |first166=Stacey |last167=Gan |first167=Weiniu |last168=Gao |first168=Shanshan |last169=Gao |first169=Yan |last170=Gass |first170=Margery |last171=Geiger |first171=Heather |last172=Gelb |first172=Bruce |last173=Geraci |first173=Mark |last174=Germer |first174=Soren |last175=Gerszten |first175=Robert |last176=Ghosh |first176=Auyon |last177=Gibbs |first177=Richard |last178=Gignoux |first178=Chris |last179=Gladwin |first179=Mark |last180=Glahn |first180=David |last181=Gogarten |first181=Stephanie |last182=Gong |first182=Da-Wei |last183=Graw |first183=Sharon |last184=Gray |first184=Kathryn J. |last185=Grine |first185=Daniel |last186=Gross |first186=Colin |last187=Gu |first187=C. Charles |last188=Guan |first188=Yue |last189=Gupta |first189=Namrata |last190=Hall |first190=Michael |last191=Han |first191=Yi |last192=Hanly |first192=Patrick |last193=Harris |first193=Daniel |last194=Hawley |first194=Nicola L. |last195=He |first195=Jiang |last196=Heavner |first196=Ben |last197=Heckbert |first197=Susan |last198=Hernandez |first198=Ryan |last199=Herrington |first199=David |last200=Hersh |first200=Craig |last201=Hidalgo |first201=Bertha |last202=Hixson |first202=James |last203=Hobbs |first203=Brian |last204=Hokanson |first204=John |last205=Hong |first205=Elliott |last206=Hoth |first206=Karin |last207=Hsiung |first207=Chao |last208=Hu |first208=Jianhong |last209=Hung |first209=Yi-Jen |last210=Huston |first210=Haley |last211=Hwu |first211=Chii Min |last212=Irvin |first212=Marguerite Ryan |last213=Jackson |first213=Rebecca |last214=Jain |first214=Deepti |last215=Jaquish |first215=Cashell |last216=Johnsen |first216=Jill |last217=Johnson |first217=Andrew |last218=Johnson |first218=Craig |last219=Johnston |first219=Rich |last220=Jones |first220=Kimberly |last221=Kang |first221=Hyun Min |last222=Kaplan |first222=Robert |last223=Kardia |first223=Sharon |last224=Kelly |first224=Shannon |last225=Kenny |first225=Eimear |last226=Kessler |first226=Michael |last227=Khan |first227=Alyna |last228=Khan |first228=Ziad |last229=Kim |first229=Wonji |last230=Kimoff |first230=John |last231=Kinney |first231=Greg |last232=Konkle |first232=Barbara |last233=Kramer |first233=Holly |last234=Lange |first234=Christoph |last235=Lange |first235=Ethan |last236=Laurie |first236=Cathy |last237=Laurie |first237=Cecelia |last238=LeBoff |first238=Meryl |last239=Lee |first239=Jiwon |last240=Lee |first240=Sandra |last241=Lee |first241=Wen-Jane |last242=LeFaive |first242=Jonathon |last243=Levine |first243=David |last244=Lewis |first244=Joshua |last245=Li |first245=Xiaohui |last246=Li |first246=Yun |last247=Lin |first247=Henry |last248=Lin |first248=Honghuang |last249=Liu |first249=Simin |last250=Liu |first250=Yongmei |last251=Liu |first251=Yu |last252=Loos |first252=Ruth J. F. |last253=Lubitz |first253=Steven |last254=Lunetta |first254=Kathryn |last255=Luo |first255=James |last256=Magalang |first256=Ulysses |last257=Mahaney |first257=Michael |last258=Make |first258=Barry |last259=Manson |first259=JoAnn |last260=Marton |first260=Melissa |last261=Mathai |first261=Susan |last262=May |first262=Susanne |last263=McArdle |first263=Patrick |last264=McDonald |first264=Merry-Lynn |last265=McFarland |first265=Sean |last266=McGoldrick |first266=Daniel |last267=McHugh |first267=Caitlin |last268=McNeil |first268=Becky |last269=Mei |first269=Hao |last270=Menon |first270=Vipin |last271=Mestroni |first271=Luisa |last272=Metcalf |first272=Ginger |last273=Meyers |first273=Deborah A. |last274=Mignot |first274=Emmanuel |last275=Mikulla |first275=Julie |last276=Min |first276=Nancy |last277=Minear |first277=Mollie |last278=Minster |first278=Ryan L. |last279=Moll |first279=Matt |last280=Momin |first280=Zeineen |last281=Montgomery |first281=Courtney |last282=Muzny |first282=Donna |last283=Mychaleckyj |first283=Josyf C. |last284=Nadkarni |first284=Girish |last285=Naik |first285=Rakhi |last286=Nekhai |first286=Sergei |last287=Nelson |first287=Sarah C. |last288=Neltner |first288=Bonnie |last289=Nessner |first289=Caitlin |last290=Nickerson |first290=Deborah |last291=Nkechinyere |first291=Osuji |last292=North |first292=Kari |last293=O'Connor |first293=Tim |last294=Ochs-Balcom |first294=Heather |last295=Okwuonu |first295=Geoffrey |last296=Pack |first296=Allan |last297=Paik |first297=David T. |last298=Pankow |first298=James |last299=Papanicolaou |first299=George |last300=Parker |first300=Cora |last301=Peralta |first301=Juan Manuel |last302=Perez |first302=Marco |last303=Perry |first303=James |last304=Peters |first304=Ulrike |last305=Phillips |first305=Lawrence S. |last306=Pleiness |first306=Jacob |last307=Pollin |first307=Toni |last308=Post |first308=Wendy |last309=Becker |first309=Julia Powers |last310=Boorgula |first310=Meher Preethi |last311=Preuss |first311=Michael |last312=Qasba |first312=Pankaj |last313=Qiao |first313=Dandi |last314=Qin |first314=Zhaohui |last315=Rafaels |first315=Nicholas |last316=Rajendran |first316=Mahitha |last317=Rao |first317=D. C. |last318=Rasmussen-Torvik |first318=Laura |last319=Ratan |first319=Aakrosh |last320=Reed |first320=Robert |last321=Reeves |first321=Catherine |last322=Regan |first322=Elizabeth |last323=Robillard |first323=Rebecca |last324=Robine |first324=Nicolas |last325=Roden |first325=Dan |last326=Roselli |first326=Carolina |last327=Ruczinski |first327=Ingo |last328=Runnels |first328=Alexi |last329=Russell |first329=Pamela |last330=Ruuska |first330=Sarah |last331=Ryan |first331=Kathleen |last332=Sabino |first332=Ester Cerdeira |last333=Saleheen |first333=Danish |last334=Salimi |first334=Shabnam |last335=Salvi |first335=Sejal |last336=Salzberg |first336=Steven |last337=Sandow |first337=Kevin |last338=Sankaran |first338=Vijay G. |last339=Santibanez |first339=Jireh |last340=Schwander |first340=Karen |last341=Schwartz |first341=David |last342=Sciurba |first342=Frank |last343=Seidman |first343=Christine |last344=Seidman |first344=Jonathan |last345=Sériès |first345=Frédéric |last346=Sheehan |first346=Vivien |last347=Sherman |first347=Stephanie L. |last348=Shetty |first348=Amol |last349=Shetty |first349=Aniket |last350=Sheu |first350=Wayne Hui-Heng |last351=Shoemaker |first351=M. Benjamin |last352=Silver |first352=Brian |last353=Silverman |first353=Edwin |last354=Skomro |first354=Robert |last355=Smith |first355=Albert Vernon |last356=Smith |first356=Josh |last357=Smith |first357=Nicholas |last358=Smith |first358=Tanja |last359=Smoller |first359=Sylvia |last360=Snively |first360=Beverly |last361=Snyder |first361=Michael |last362=Sofer |first362=Tamar |last363=Sotoodehnia |first363=Nona |last364=Stilp |first364=Adrienne M. |last365=Storm |first365=Garrett |last366=Streeten |first366=Elizabeth |last367=Su |first367=Jessica Lasky |last368=Sung |first368=Yun Ju |last369=Sylvia |first369=Jody |last370=Szpiro |first370=Adam |last371=Taliun |first371=Daniel |last372=Tang |first372=Hua |last373=Taub |first373=Margaret |last374=Taylor |first374=Matthew |last375=Taylor |first375=Simeon |last376=Telen |first376=Marilyn |last377=Thornton |first377=Timothy A. |last378=Threlkeld |first378=Machiko |last379=Tinker |first379=Lesley |last380=Tirschwell |first380=David |last381=Tishkoff |first381=Sarah |last382=Tiwari |first382=Hemant |last383=Tong |first383=Catherine |last384=Tracy |first384=Russell |last385=Tsai |first385=Michael |last386=Vaidya |first386=Dhananjay |last387=Van Den Berg |first387=David |last388=VandeHaar |first388=Peter |last389=Vrieze |first389=Scott |last390=Walker |first390=Tarik |last391=Wallace |first391=Robert |last392=Walts |first392=Avram |last393=Wang |first393=Fei Fei |last394=Wang |first394=Heming |last395=Wang |first395=Jiongming |last396=Watson |first396=Karol |last397=Watt |first397=Jennifer |last398=Weinstock |first398=Joshua |last399=Weir |first399=Bruce |last400=Weiss |first400=Scott T. |last401=Weng |first401=Lu-Chen |last402=Wessel |first402=Jennifer |last403=Williams |first403=Kayleen |last404=Williams |first404=L. Keoki |last405=Wilson |first405=Carla |last406=Winterkorn |first406=Lara |last407=Wong |first407=Quenna |last408=Wu |first408=Joseph |last409=Xu |first409=Huichun |last410=Yang |first410=Ivana |last411=Yu |first411=Ketian |last412=Zekavat |first412=Seyedeh Maryam |last413=Zhang |first413=Yingze |last414=Zhao |first414=Snow Xueyan |last415=Zhu |first415=Xiaofeng |last416=Ziv |first416=Elad |last417=Zody |first417=Michael |last418=Zoellner |first418=Sebastian |last419=Atkinson |first419=Elizabeth |last420=Ballantyne |first420=Christie |last421=Bao |first421=Wei |last422=Bhattacharya |first422=Romit |last423=Bielak |first423=Larry |last424=Bis |first424=Joshua |last425=Bodea |first425=Corneliu |last426=Brody |first426=Jennifer |last427=Cade |first427=Brian |last428=Calvo |first428=Sarah |last429=Carlson |first429=Jenna |last430=Chang |first430=I-Shou |last431=Cho |first431=So Mi |last432=de Vries |first432=Paul |last433=Diallo |first433=Ana F. |last434=Do |first434=Ron |last435=Dron |first435=Jacqueline |last436=Elliott |first436=Amanda |last437=Finucane |first437=Hilary |last438=Floyd |first438=Caitlin |last439=Ganna |first439=Andrea |last440=Gong |first440=Dawei |last441=Graham |first441=Sarah |last442=Haas |first442=Mary |last443=Haring |first443=Bernhard |last444=Heemann |first444=Scott |last445=Himes |first445=Blanca |last446=Jarvik |first446=Gail |last447=Jiang |first447=Jicai |last448=Joehanes |first448=Roby |last449=Joseph |first449=Paule Valery |last450=Jun |first450=Goo |last451=Kalyani |first451=Rita |last452=Kanai |first452=Masahiro |last453=Kathiresan |first453=Sekar |last454=Khera |first454=Amit |last455=Khetarpal |first455=Sumeet |last456=Klarin |first456=Derek |last457=Koyama |first457=Satoshi |last458=Kral |first458=Brian |last459=Lange |first459=Leslie |last460=Lemaitre |first460=Rozenn |last461=Li |first461=Changwei |last462=Lu |first462=Yingchang |last463=Martin |first463=Lisa |last464=Mathias |first464=Rasika |last465=Mathur |first465=Ravi |last466=McGarvey |first466=Stephen |last467=McLenithan |first467=John |last468=Miller |first468=Amy |last469=Mootha |first469=Vamsi |last470=Moran |first470=Andrew |last471=Nakao |first471=Tetsushi |last472=O'Connell |first472=Jeff |last473=O'Donnell |first473=Christopher |last474=Palmer |first474=Nicholette |last475=Paruchuri |first475=Kaavya |last476=Patel |first476=Aniruddh |last477=Peloso |first477=Gina |last478=Pettinger |first478=Mary |last479=Peyser |first479=Patricia |last480=Pirruccello |first480=James |last481=Psaty |first481=Bruce |last482=Reiner |first482=Alex |last483=Rich |first483=Stephen |last484=Rosenthal |first484=Samantha |last485=Rotter |first485=Jerome |last486=Smith |first486=Jennifer |last487=Sunyaev |first487=Shamil R. |last488=Surakka |first488=Ida |last489=Sztalryd |first489=Carole |last490=Trinder |first490=Mark |last491=Uddin |first491=Md Mesbah |last492=Urbut |first492=Sarah |last493=Van Buren |first493=Eric |last494=Verbanck |first494=Marie |last495=Von Holle |first495=Ann |last496=Wang |first496=Yuxuan |last497=Wiggins |first497=Kerri |last498=Wilkins |first498=John |last499=Willer |first499=Cristen |last500=Wilson |first500=James |last501=Wolford |first501=Brooke |last502=Yanek |first502=Lisa |last503=Yu |first503=Zhi |last504=Zaghloul |first504=Norann |last505=Zhang |first505=Jingwen |last506=Zhou |first506=Ying |last507=Rotter |first507=Jerome I. |last508=Willer |first508=Cristen J. |last509=Natarajan |first509=Pradeep |last510=Peloso |first510=Gina M. |last511=Lin |first511=Xihong|title=A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies |journal=Nature Methods |date=December 2022 |volume=19 |issue=12 |pages=1599–1611 |doi=10.1038/s41592-022-01640-x|pmid=36303018 |pmc=10008172 |s2cid=243873361 }}</ref><ref>{{cite journal |title=STAARpipeline: an all-in-one rare-variant tool for biobank-scale whole-genome sequencing data |journal=Nature Methods |date=December 2022 |volume=19 |issue=12 |pages=1532–1533 |doi=10.1038/s41592-022-01641-w|pmid=36316564 |s2cid=253246835 }}</ref> Meta-analysis of whole genome sequencing studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes.<ref>{{cite journal |last1=Li |first1=Xihao |last2=Quick |first2=Corbin |last3=Zhou |first3=Hufeng |last4=Gaynor |first4=Sheila M. |last5=Liu |first5=Yaowu |last6=Chen |first6=Han |last7=Selvaraj |first7=Margaret Sunitha |last8=Sun |first8=Ryan |last9=Dey |first9=Rounak |last10=Arnett |first10=Donna K. |last11=Bielak |first11=Lawrence F. |last12=Bis |first12=Joshua C. |last13=Blangero |first13=John |last14=Boerwinkle |first14=Eric |last15=Bowden |first15=Donald W. |last16=Brody |first16=Jennifer A. |last17=Cade |first17=Brian E. |last18=Correa |first18=Adolfo |last19=Cupples |first19=L. Adrienne |last20=Curran |first20=Joanne E. |last21=de Vries |first21=Paul S. |last22=Duggirala |first22=Ravindranath |last23=Freedman |first23=Barry I. |last24=Göring |first24=Harald H. H. |last25=Guo |first25=Xiuqing |last26=Haessler |first26=Jeffrey |last27=Kalyani |first27=Rita R. |last28=Kooperberg |first28=Charles |last29=Kral |first29=Brian G. |last30=Lange |first30=Leslie A. |last31=Manichaikul |first31=Ani |last32=Martin |first32=Lisa W. |last33=McGarvey |first33=Stephen T. |last34=Mitchell |first34=Braxton D. |last35=Montasser |first35=May E. |last36=Morrison |first36=Alanna C. |last37=Naseri |first37=Take |last38=O'Connell |first38=Jeffrey R. |last39=Palmer |first39=Nicholette D. |last40=Peyser |first40=Patricia A. |last41=Psaty |first41=Bruce M. |last42=Raffield |first42=Laura M. |last43=Redline |first43=Susan |last44=Reiner |first44=Alexander P. |last45=Reupena |first45=Muagututi'a Sefuiva |last46=Rice |first46=Kenneth M. |last47=Rich |first47=Stephen S. |last48=Sitlani |first48=Colleen M. |last49=Smith |first49=Jennifer A. |last50=Taylor |first50=Kent D. |last51=Vasan |first51=Ramachandran S. |last52=Willer |first52=Cristen J. |last53=Wilson |first53=James G. |last54=Yanek |first54=Lisa R. |last55=Zhao |first55=Wei |last56=NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium|last57=TOPMed Lipids Working Group

|last58=Rotter |first58=Jerome I. |last59=Natarajan |first59=Pradeep |last60=Peloso |first60=Gina M. |last61=Li |first61=Zilin |last62=Lin |first62=Xihong |title=Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies |journal=Nature Genetics |date=January 2023 |volume=55 |issue=1 |pages=154–164 |doi=10.1038/s41588-022-01225-6|pmid=36564505 |pmc=10084891 |s2cid=255084231 }}</ref>

Line 115 ⟶ 114:

{{main|Oncogenomics}}

In [[cancer]], the genomes of affected cells are rearranged in complex or unpredictable ways. In addition to [[single-nucleotide polymorphism]] arrays identifying [[point mutation]]s that cause cancer, [[oligonucleotide]] microarrays can be used to identify chromosomal gains and losses (called [[comparative genomic hybridization]]). These detection methods generate [[terabyte]]s of data per experiment.<ref>{{cite arXiv | last1=Tsourakakis | first1=Charalampos E. | last2=Tolliver | first2=David | last3=Tsiarli | first3=Maria A. | last4=Shackney | first4=Stanley | last5=Schwartz | first5=Russell | title=CGHTRIMMER: Discretizing noisy Array CGH Data | date=2010 | class=q-bio.GN | eprint=1002.4438 }}</ref> The data is often found to contain considerable variability, or [[noise]], and thus [[Hidden Markov model]] and change-point analysis methods are being developed to infer real [[copy number]] changes.<ref>{{Citationcite journal needed| last1=Berezovsky | first1=Igor N. | last2=Zeldovich | first2=Konstantin B. | last3=Shakhnovich | first3=Eugene I. | title=Positive and Negative Design in Stability and Thermal Adaptation of Natural Proteins | journal=PLOS Computational Biology | date=June2007 | volume=3 | issue=3 | pages=e52 | doi=10.1371/journal.pcbi.0030052 | pmid=17381236 | pmc=1829478 | arxiv=q-bio/0607003 | bibcode=2007PLSCB...3...52B | doi-access=free 2023}}</ref>

Two important principles can be used to identify cancer by mutations in the [[exome]]. First, cancer is a disease of accumulated somatic mutations in genes. Second, cancer contains driver mutations which need to be distinguished from passengers.<ref>{{cite journal | vauthors = Vazquez M, de la Torre V, Valencia A | title = Chapter 14: Cancer genome analysis | journal = PLOS Computational Biology | volume = 8 | issue = 12 | pages = e1002824 | date = 2012-12-27 | pmid = 23300415 | pmc = 3531315 | doi = 10.1371/journal.pcbi.1002824 | bibcode = 2012PLSCB...8E2824V | doi-access = free }}</ref>

Line 159 ⟶ 158:

=== Amino acid sequence ===

The linear [[amino acid]] sequence of a protein is called the [[primary structure]]. The primary structure can be easily determined from the sequence of [[codons]] on the DNA gene that codes for it. In most proteins, the primary structure uniquely determines the 3-dimensional structure of a protein in its native environment. An exception is the [[Prion|misfolded protein[[prion]] protein involved in [[bovine spongiform encephalopathy]]. This structure is linked to the function of the protein. Additional structural information includes the ''[[secondary structure|secondary]]'', ''[[tertiary structure|tertiary]]'' and ''[[quaternary structure|quaternary]]'' structure. A viable general solution to the prediction of the function of a protein remains an open problem. Most efforts have so far been directed towards heuristics that work most of the time.{{citation needed|date=July 2015}}

=== Homology ===

In the genomic branch of bioinformatics, homology is used to predict the function of a gene: if the sequence of gene ''A'', whose function is known, is homologous to the sequence of gene ''B,'' whose function is unknown, one could infer that B may share A's function. In structural bioinformatics, homology is used to determine which parts of a protein are important in structure formation and interaction with other proteins. [[Homology modeling]] is used to predict the structure of an unknown protein from existing homologous proteins.

One example of this is hemoglobin in humans and the hemoglobin in legumes ([[leghemoglobin]]), which are distant relatives from the same [[protein superfamily]]. Both serve the same purpose of transporting oxygen in the organism. Although both of these proteins have completelyvery different amino acid sequences, their protein structures are virtuallyvery identicalsimilar, which reflectsreflecting their near identicalshared purposesfunction and shared ancestor.<ref>{{cite journal | vauthors = Hoy JA, Robinson H, Trent JT, Kakar S, Smagghe BJ, Hargrove MS | title = Plant hemoglobins: a molecular fossil record for the evolution of oxygen transport | journal = Journal of Molecular Biology | volume = 371 | issue = 1 | pages = 168–79 | date = August 2007 | pmid = 17560601 | doi = 10.1016/j.jmb.2007.05.029 }}</ref>

Other techniques for predicting protein structure include protein threading and ''de novo'' (from scratch) physics-based modeling.

Line 170 ⟶ 169:

Another aspect of structural bioinformatics include the use of protein structures for [[Virtual screening|Virtual Screening]] models such as [[Quantitative Structure-Activity Relationship]] models and proteochemometric models (PCM). Furthermore, a protein's crystal structure can be used in simulation of for example ligand-binding studies and ''in silico'' mutagenesis studies.

A 2021 [[deep-learning]] algorithms-based software called [[AlphaFold]], developed by Google's [[DeepMind]], greatly outperforms all other prediction software methods,<ref>{{Cite journal |last1=Jumper |first1=John |last2=Evans |first2=Richard |last3=Pritzel |first3=Alexander |last4=Green |first4=Tim |last5=Figurnov |first5=Michael |last6=Ronneberger |first6=Olaf |last7=Tunyasuvunakool |first7=Kathryn |last8=Bates |first8=Russ |last9=Žídek |first9=Augustin |last10=Potapenko |first10=Anna |last11=Bridgland |first11=Alex |last12=Meyer |first12=Clemens |last13=Kohl |first13=Simon A. A. |last14=Ballard |first14=Andrew J. |last15=Cowie |first15=Andrew |date=August 2021 |title=Highly accurate protein structure prediction with AlphaFold |journal=Nature |language=en |volume=596 |issue=7873 |pages=583–589 |bibcode=2021Natur.596..583J |doi=10.1038/s41586-021-03819-2 |issn=1476-4687 |pmc=8371605 |pmid=34265844}}</ref>{{How|date=June 2023}}, and has released predicted structures for hundreds of millions of proteins in the AlphaFold protein structure database.<ref>{{Cite web |title=AlphaFold Protein Structure Database |url=https://alphafold.ebi.ac.uk/ |access-date=2022-10-10 |website=alphafold.ebi.ac.uk |archive-date=24 July 2021 |archive-url=https://web.archive.org/web/20210724013505/https://alphafold.ebi.ac.uk/ |url-status=live }}</ref>

==Network and systems biology==

Line 241 ⟶ 240:

===Open-source bioinformatics software===

{{Main articles| List of open-source bioinformatics software}}

{{See also|List of bioinformatics software}}

Many [[free and open-source software]] tools have existed and continued to grow since the 1980s.<ref name="obf-main">{{cite web |title=Open Bioinformatics Foundation: About us |url=http://www.open-bio.org/wiki/Main_Page |website=Official website |publisher=[[Open Bioinformatics Foundation]] |access-date=10 May 2011 |archive-date=12 May 2011 |archive-url=https://web.archive.org/web/20110512022059/http://open-bio.org/wiki/Main_Page |url-status=live }}</ref> The combination of a continued need for new [[algorithm]]s for the analysis of emerging types of biological readouts, the potential for innovative ''[[in silico]]'' experiments, and freely available [[open code]] bases have created opportunities for research groups to contribute to both bioinformatics regardless of [[Funding of science|funding]]. The open source tools often act as incubators of ideas, or community-supported [[Plug-in (computing)|plug-ins]] in commercial applications. They may also provide ''[[de facto]]'' standards and shared object models for assisting with the challenge of bioinformation integration.

Line 267:

=== BioCompute and BioCompute Objects ===

In 2014, the [[US Food and Drug Administration]] sponsored a conference held at the [[National Institutes of Health]] Bethesda Campus to discuss reproducibility in bioinformatics.<ref>{{Cite web|url=https://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm389561.htm|title=Advancing Regulatory Science – Sept. 24–25, 2014 Public Workshop: Next Generation Sequencing Standards|author=Office of the Commissioner|website=www.fda.gov|language=en|access-date=2017-11-30|archive-date=14 November 2017|archive-url=https://web.archive.org/web/20171114200347/https://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm389561.htm|url-status=livedead}}</ref> Over the next three years, a consortium of stakeholders met regularly to discuss what would become BioCompute paradigm.<ref>{{cite journal | vauthors = Simonyan V, Goecks J, Mazumder R | title = Biocompute Objects-A Step towards Evaluation and Validation of Biomedical Scientific Computations | journal = PDA Journal of Pharmaceutical Science and Technology | volume = 71 | issue = 2 | pages = 136–146 | date = 2017 | pmid = 27974626 | pmc = 5510742 | doi = 10.5731/pdajpst.2016.006734 }}</ref> These stakeholders included representatives from government, industry, and academic entities. Session leaders represented numerous branches of the FDA and NIH Institutes and Centers, non-profit entities including the [[Human Variome Project]] and the [[European Federation for Medical Informatics]], and research institutions including [[Stanford]], the [[New York Genome Center]], and the [[George Washington University]].

It was decided that the BioCompute paradigm would be in the form of digital 'lab notebooks' which allow for the reproducibility, replication, review, and reuse, of bioinformatics protocols. This was proposed to enable greater continuity within a research group over the course of normal personnel flux while furthering the exchange of ideas between groups. The US FDA funded this work so that information on pipelines would be more transparent and accessible to their regulatory staff.<ref>{{Cite web|url=https://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm491893.htm|title=Advancing Regulatory Science – Community-based development of HTS standards for validating data and computation and encouraging interoperability|author=Office of the Commissioner|website=www.fda.gov|language=en|access-date=2017-11-30|archive-date=26 January 2018|archive-url=https://web.archive.org/web/20180126133504/https://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm491893.htm|url-status=livedead}}</ref>

In 2016, the group reconvened at the NIH in Bethesda and discussed the potential for a [[BioCompute Object]], an instance of the BioCompute paradigm. This work was copied as both a "standard trial use" document and a preprint paper uploaded to bioRxiv. The BioCompute object allows for the JSON-ized record to be shared among employees, collaborators, and regulators.<ref>{{cite journal | vauthors = Alterovitz G, Dean D, Goble C, Crusoe MR, Soiland-Reyes S, Bell A, Hayes A, Suresh A, Purkayastha A, King CH, Taylor D, Johanson E, Thompson EE, Donaldson E, Morizono H, Tsang H, Vora JK, Goecks J, Yao J, Almeida JS, Keeney J, Addepalli K, Krampis K, Smith KM, Guo L, Walderhaug M, Schito M, Ezewudo M, Guimera N, Walsh P, Kahsay R, Gottipati S, Rodwell TC, Bloom T, Lai Y, Simonyan V, Mazumder R | title = Enabling precision medicine via standard communication of HTS provenance, analysis, and results | journal = PLOS Biology | volume = 16 | issue = 12 | pages = e3000099 | date = December 2018 | pmid = 30596645 | doi = 10.1371/journal.pbio.3000099 | pmc = 6338479 | doi-access = free }}</ref><ref>{{Citation|title=BioCompute Object (BCO) project is a collaborative and community-driven framework to standardize HTS computational data. 1. BCO Specification Document: user manual for understanding and creating B.|date=2017-09-03|url=https://github.com/biocompute-objects/HTS-CSRS|publisher=biocompute-objects|access-date=30 November 2017|archive-date=27 June 2018|archive-url=https://web.archive.org/web/20180627081221/https://github.com/biocompute-objects/HTS-CSRS|url-status=live}}</ref>

==Education platforms==

BioinformaticsWhile isbioinformatics not onlyis taught as an in-person [[mastersmaster's degree]] at many universities, there are many other methods and technologies available to learn and obtain certification in the subject. The computational nature of bioinformatics lends it to [[Educational technology|computer-aided and online learning]].<ref>{{Cite journal |last=Campbell |first=A. Malcolm |date=2003-06-01 |title=Public Access for Teaching Genomics, Proteomics, and Bioinformatics |journal=Cell Biology Education |volume=2 |issue=2 |pages=98–111 |doi=10.1187/cbe.03-02-0007 |pmc=162192 |pmid=12888845}}</ref><ref>{{Cite journal |last=Arenas |first=Miguel |date=September 2021 |title=General considerations for online teaching practices in bioinformatics in the time of COVID -19 |journal=Biochemistry and Molecular Biology Education |language=en |volume=49 |issue=5 |pages=683–684 |doi=10.1002/bmb.21558 |issn=1470-8175 |pmc=8426940 |pmid=34231941}}</ref> Software platforms designed to teach bioinformatics concepts and methods include [[Rosalind (education platform)|Rosalind]] and online courses offered through the [[Swiss Institute of Bioinformatics]] Training Portal. The [[Canadian Bioinformatics Workshops]] provides videos and slides from training workshops on their website under a [[Creative Commons]] license. The 4273π project or 4273pi project<ref>{{cite journal | vauthors = Barker D, Ferrier DE, Holland PW, Mitchell JB, Plaisier H, Ritchie MG, Smart SD | title = 4273π: bioinformatics education on low cost ARM hardware | journal = BMC Bioinformatics | volume = 13 | pages = 522 | date = August 2013 | pmid = 23937194 | pmc = 3751261 | doi = 10.1186/1471-2105-14-243 | doi-access = free }}</ref> also offers open source educational materials for free. The course runs on low cost [[Raspberry Pi]] computers and has been used to teach adults and school pupils.<ref>{{cite journal | vauthors = Barker D, Alderson RG, McDonagh JL, Plaisier H, Comrie MM, Duncan L, Muirhead GT, Sweeney SD |title=University-level practical activities in bioinformatics benefit voluntary groups of pupils in the last 2 years of school |journal=International Journal of STEM Education |date=2015 |volume=2 |issue=17 |doi=10.1186/s40594-015-0030-z | s2cid = 256396656 |hdl=10023/7704 |hdl-access=free | doi-access = free }}</ref><ref>{{cite journal | vauthors = McDonagh JL, Barker D, Alderson RG | title = Bringing computational science to the public | journal = SpringerPlus | volume = 5 | issue = 259 | pages = 259 | date = 2016 | pmid = 27006868 | pmc = 4775721 | doi = 10.1186/s40064-016-1856-7 | doi-access = free }}</ref> 4273 is actively developed by a consortium of academics and research staff who have run research level bioinformatics using Raspberry Pi computers and the 4273π operating system.<ref>{{cite journal | vauthors = Robson JF, Barker D | title = Comparison of the protein-coding gene content of Chlamydia trachomatis and Protochlamydia amoebophila using a Raspberry Pi computer | journal = BMC Research Notes | volume = 8 | issue = 561 | pages = 561 | date = October 2015 | pmid = 26462790 | pmc = 4604092 | doi = 10.1186/s13104-015-1476-2 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wreggelsworth KM, Barker D | title = A comparison of the protein-coding genomes of two green sulphur bacteria, Chlorobium tepidum TLS and Pelodictyon phaeoclathratiforme BU-1 | journal = BMC Research Notes | volume = 8 | issue = 565 | pages = 565 | date = October 2015 | pmid = 26467441 | pmc = 4606965 | doi = 10.1186/s13104-015-1535-8 | doi-access = free }}</ref>

[[MOOC]] platforms also provide online certifications in bioinformatics and related disciplines, including [[Coursera]]'s Bioinformatics Specialization at the [[University of California, San Diego]], Genomic Data Science Specialization at [[Johns Hopkins University]], and [[EdX]]'s Data Analysis for Life Sciences XSeries at [[Harvard University]].

Line 290:

* [[Computational genomics]]

* [[Cyberbiosecurity]]

* [[Earth BioGenome Project]]

* [[Functional genomics]]

* [[Gene Disease Database]]