John Anthony Capra, Ph.D.

Associate Professor

tony.capra@vanderbilt.edu

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Faculty Appointments
Associate Professor of Biological Sciences Assistant Professor of Computer ScienceAssociate Professor of Biomedical Informatics
Education
Ph.D., Computer Science, Princeton University, Princeton, New JerseyM.A., Computer Science, Princeton University, Princeton, New JerseyB.A., Computer Science & Mathematics, Columbia University, New York, New York
Office Address
VU Station B, Box 35-1634
Department of Biological Sciences
Nashville, TN 37235
Research Description
My group compares genomes to study recent human evolution and disease.

Humans differ from one another and our closest living relatives, the chimpanzees, in a wide range of traits, including our susceptibility to many diseases. We model the evolutionary processes that have produced these novel traits and develop machine learning algorithms that compare genomes to predict the functional relevance of specific genetic differences between individuals and species.

Our research is motivated by several questions:

How have evolutionary processes produced the astonishing diversity of form and function present in the natural world?

How can our increasing knowledge of genomic variation be translated into the treatment and prevention of disease?

How can better algorithms lead to a deeper understanding of biological systems and networks?

How do genomes encode and maintain the information necessary to produce life?

We investigate these questions in a number of model systems, but our main focus is on the origins and recent evolution of human populations and their primate relatives.
Research Keywords
bioinformatics; genomics; evolution; machine learning; gene regulation; precision medicine; computational biology; structural biology; Neanderthal; biovu
Publications
Marinko JT, Huang H, Penn WD, Capra JA, Schlebach JP, Sanders CR. Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis. Chem. Rev [print-electronic]. 2019 May 5/8/2019; 119(9): 5537-606. PMID: 30608666, PMCID: PMC6506414, DOI: 10.1021/acs.chemrev.8b00532, ISSN: 1520-6890.

Colbran LL, Chen L, Capra JA. Sequence Characteristics Distinguish Transcribed Enhancers from Promoters and Predict Their Breadth of Activity. Genetics [print-electronic]. 2019 Apr; 211(4): 1205-17. PMID: 30696717, PMCID: PMC6456323, PII: genetics.118.301895, DOI: 10.1534/genetics.118.301895, ISSN: 1943-2631.

Kroncke BM, Mendenhall J, Smith DK, Sanders CR, Capra JA, George AL, Blume JD, Meiler J, Roden DM. Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1. Comput Struct Biotechnol J. 2019; 17: 206-14. PMID: 30828412, PMCID: PMC6383132, PII: S2001-0370(18)30270-8, DOI: 10.1016/j.csbj.2019.01.008, ISSN: 2001-0370.

Eidem HR, Steenwyk JL, Wisecaver JH, Capra JA, Abbot P, Rokas A. IntegRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth. BMC Med Genomics. 2018 Nov 11/19/2018; 11(1): 107. PMID: 30453955, PMCID: PMC6245874, PII: 10.1186/s12920-018-0426-y, DOI: 10.1186/s12920-018-0426-y, ISSN: 1755-8794.

Chen L, Fish AE, Capra JA. Prediction of gene regulatory enhancers across species reveals evolutionarily conserved sequence properties. PLoS Comput. Biol. 2018 Oct; 14(10): e1006484. PMID: 30286077, PMCID: PMC6191148, PII: PCOMPBIOL-D-18-00343, DOI: 10.1371/journal.pcbi.1006484, ISSN: 1553-7358.

Sivley RM, Dou X, Meiler J, Bush WS, Capra JA. Comprehensive Analysis of Constraint on the Spatial Distribution of Missense Variants in Human Protein Structures. Am. J. Hum. Genet [print-electronic]. 2018 Mar 3/1/2018; 102(3): 415-26. PMID: 29455857, PII: S0002-9297(18)30039-9, DOI: 10.1016/j.ajhg.2018.01.017, ISSN: 1537-6605.

Moon JM, Aronoff DM, Capra JA, Abbot P, Rokas A. Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology. G3 (Bethesda) [print-electronic]. 2018 Feb 2/21/2018; PMID: 29467190, PII: g3.118.200035, DOI: 10.1534/g3.118.200035, ISSN: 2160-1836.

Sivley RM, Sheehan JH, Kropski JA, Cogan J, Blackwell TS, Phillips JA, Bush WS, Meiler J, Capra JA. Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia. BMC Bioinformatics. 2018 Jan 1/23/2018; 19(1): 18. PMID: 29361909, PMCID: PMC5781290, PII: 10.1186/s12859-018-2010-z, DOI: 10.1186/s12859-018-2010-z, ISSN: 1471-2105.

Fish AE, Crawford DC, Capra JA, Bush WS. Local ancestry transitions modify snp-trait associations. Pac Symp Biocomput. 2018; 23: 424-35. PMID: 29218902, PMCID: PMC5728664, PII: 9789813235533_0039, ISSN: 2335-6936.

Zhang J, Simonti CN, Capra JA. Genome-wide maps of distal gene regulatory enhancers active in the human placenta. PLoS ONE. 2018; 13(12): e0209611. PMID: 30589856, PMCID: PMC6320013, PII: PONE-D-18-20998, DOI: 10.1371/journal.pone.0209611, ISSN: 1932-6203.

Simonti CN, Pavlicev M, Capra JA. Transposable Element Exaptation into Regulatory Regions Is Rare, Influenced by Evolutionary Age, and Subject to Pleiotropic Constraints. Mol. Biol. Evol. 2017 Nov 11/1/2017; 34(11): 2856-69. PMID: 28961735, PII: 4082767, DOI: 10.1093/molbev/msx219, ISSN: 1537-1719.

Fish A, Chen L, Capra JA. Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity. Genome Biol Evol. 2017 Oct 10/1/2017; 9(10): 2615-25. PMID: 28985297, PMCID: PMC5737616, PII: 4161386, DOI: 10.1093/gbe/evx194, ISSN: 1759-6653.

Abbot P, Capra JA. What is a placental mammal anyway?. Elife. 2017 Sep 9/12/2017; 6: PMID: 28895533, PMCID: PMC5595430, DOI: 10.7554/eLife.30994, ISSN: 2050-084X.

Eidem HR, McGary KL, Capra JA, Abbot P, Rokas A. The transformative potential of an integrative approach to pregnancy. Placenta [print-electronic]. 2017 Sep; 57: 204-15. PMID: 28864013, PII: S0143-4004(17)30659-8, DOI: 10.1016/j.placenta.2017.07.010, ISSN: 1532-3102.

Patel VD, Capra JA. Ancient human miRNAs are more likely to have broad functions and disease associations than young miRNAs. BMC Genomics. 2017 Aug 8/31/2017; 18(1): 672. PMID: 28859623, PMCID: PMC5579935, PII: 10.1186/s12864-017-4073-z, DOI: 10.1186/s12864-017-4073-z, ISSN: 1471-2164.

Colbran LL, Chen L, Capra JA. Short DNA sequence patterns accurately identify broadly active human enhancers. BMC Genomics. 2017 Jul 7/17/2017; 18(1): 536. PMID: 28716036, PMCID: PMC5512948, PII: 10.1186/s12864-017-3934-9, DOI: 10.1186/s12864-017-3934-9, ISSN: 1471-2164.

Wanzek K, Schwindt E, Capra JA, Paeschke K. Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability. Nucleic Acids Res [print-electronic]. 2017 May 5/23/2017; PMID: 28535251, PII: 3848402, DOI: 10.1093/nar/gkx467, ISSN: 1362-4962.

Anderson KA, Huynh FK, Fisher-Wellman K, Stuart JD, Peterson BS, Douros JD, Wagner GR, Thompson JW, Madsen AS, Green MF, Sivley RM, Ilkayeva OR, Stevens RD, Backos DS, Capra JA, Olsen CA, Campbell JE, Muoio DM, Grimsrud PA, Hirschey MD. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017 Apr 4/4/2017; 25(4): 838-855.e15. PMID: 28380376, PMCID: PMC5444661, PII: S1550-4131(17)30154-7, DOI: 10.1016/j.cmet.2017.03.003, ISSN: 1932-7420.

Samuels DC, Wang J, Ye F, He J, Levinson RT, Sheng Q, Zhao S, Capra JA, Shyr Y, Zheng W, Guo Y. Heterozygosity Ratio, a Robust Global Genomic Measure of Autozygosity and Its Association with Height and Disease Risk. Genetics [print-electronic]. 2016 Nov; 204(3): 893-904. PMID: 27585849, PMCID: PMC5105867, PII: genetics.116.189936, DOI: 10.1534/genetics.116.189936, ISSN: 1943-2631.

Fish AE, Capra JA, Bush WS. Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?. Am. J. Hum. Genet [print-electronic]. 2016 Oct 10/6/2016; 99(4): 817-30. PMID: 27640306, PMCID: PMC5065654, PII: S0002-9297(16)30323-8, DOI: 10.1016/j.ajhg.2016.07.022, ISSN: 1537-6605.

McDonald KR, Guise AJ, Pourbozorgi-Langroudi P, Cristea IM, Zakian VA, Capra JA, Sabouri N. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity. PLoS Genet. 2016 Sep; 12(9): e1006238. PMID: 27611590, PMCID: PMC5017727, PII: PGENETICS-D-16-00019, DOI: 10.1371/journal.pgen.1006238, ISSN: 1553-7404.

Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ. XPA: A key scaffold for human nucleotide excision repair. DNA Repair (Amst.) [print-electronic]. 2016 Aug; 44: 123-35. PMID: 27247238, PMCID: PMC4958585, PII: S1568-7864(16)30098-2, DOI: 10.1016/j.dnarep.2016.05.018, ISSN: 1568-7856.

Simonti CN, Vernot B, Bastarache L, Bottinger E, Carrell DS, Chisholm RL, Crosslin DR, Hebbring SJ, Jarvik GP, Kullo IJ, Li R, Pathak J, Ritchie MD, Roden DM, Verma SS, Tromp G, Prato JD, Bush WS, Akey JM, Denny JC, Capra JA. The phenotypic legacy of admixture between modern humans and Neandertals. Science. 2016 Feb 2/12/2016; 351(6274): 737-41. PMID: 26912863, PMCID: PMC4849557, PII: 351/6274/737, DOI: 10.1126/science.aad2149, ISSN: 1095-9203.

Kim M, Cooper BA, Venkat R, Phillips JB, Eidem HR, Hirbo J, Nutakki S, Williams SM, Muglia LJ, Capra JA, Petren K, Abbot P, Rokas A, McGary KL. GEneSTATION 1.0: a synthetic resource of diverse evolutionary and functional genomic data for studying the evolution of pregnancy-associated tissues and phenotypes. Nucleic Acids Res [print-electronic]. 2016 Jan 1/4/2016; 44(D1): D908-16. PMID: 26567549, PMCID: PMC4702823, PII: gkv1137, DOI: 10.1093/nar/gkv1137, ISSN: 1362-4962.

Wang X, Pandey AK, Mulligan MK, Williams EG, Mozhui K, Li Z, Jovaisaite V, Quarles LD, Xiao Z, Huang J, Capra JA, Chen Z, Taylor WL, Bastarache L, Niu X, Pollard KS, Ciobanu DC, Reznik AO, Tishkov AV, Zhulin IB, Peng J, Nelson SF, Denny JC, Auwerx J, Lu L, Williams RW. Joint mouse-human phenome-wide association to test gene function and disease risk. Nat Commun. 2016; 7: 10464. PMID: 26833085, PMCID: PMC4740880, PII: ncomms10464, DOI: 10.1038/ncomms10464, ISSN: 2041-1723.

Simonti CN, Capra JA. The evolution of the human genome. Curr. Opin. Genet. Dev [print-electronic]. 2015 Dec; 35: 9-15. PMID: 26338498, PMCID: PMC4695266, PII: S0959-437X(15)00088-X, DOI: 10.1016/j.gde.2015.08.005, ISSN: 1879-0380.

Yu YK, Capra JA, Stojmirovic A, Landsman D, Altschul SF. Log-odds sequence logos. Bioinformatics [print-electronic]. 2015 Feb 2/1/2015; 31(3): 324-31. PMID: 25294922, PMCID: PMC4318935, PII: btu634, DOI: 10.1093/bioinformatics/btu634, ISSN: 1367-4811.

Yu YK, Capra JA, Stojmirovic A, Landsman D, Altschul SF. Log-odds sequence logos. Bioinformatics [print-electronic]. 2015 Feb 2/1/2015; 31(3): 324-31. PMID: 25294922, PMCID: PMC4318935, PII: btu634, DOI: 10.1093/bioinformatics/btu634, ISSN: 1367-4811.

Simonti CN, Pollard KS, Schröder S, He D, Bruneau BG, Ott M, Capra JA. Evolution of lysine acetylation in the RNA polymerase II C-terminal domain. BMC Evol. Biol. 2015; 15: 35. PMID: 25887984, PMCID: PMC4362643, PII: 10.1186/s12862-015-0327-z, DOI: 10.1186/s12862-015-0327-z, ISSN: 1471-2148.

Capra JA. Extrapolating histone marks across developmental stages, tissues, and species: an enhancer prediction case study. BMC Genomics. 2015; 16: 104. PMID: 25765133, PMCID: PMC4342796, PII: s12864-015-1264-3, DOI: 10.1186/s12864-015-1264-3, ISSN: 1471-2164.

Capra JA, Kostka D. Modeling DNA methylation dynamics with approaches from phylogenetics. Bioinformatics. 2014 Sep 9/1/2014; 30(17): i408-14. PMID: 25161227, PMCID: PMC4147898, PII: btu445, DOI: 10.1093/bioinformatics/btu445, ISSN: 1367-4811.

Capra JA, Kostka D. Modeling DNA methylation dynamics with approaches from phylogenetics. Bioinformatics. 2014 Sep 9/1/2014; 30(17): i408-14. PMID: 25161227, PMCID: PMC4147898, PII: btu445, DOI: 10.1093/bioinformatics/btu445, ISSN: 1367-4811.

Erwin GD, Oksenberg N, Truty RM, Kostka D, Murphy KK, Ahituv N, Pollard KS, Capra JA. Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput. Biol. 2014 Jun; 10(6): e1003677. PMID: 24967590, PMCID: PMC4072507, PII: PCOMPBIOL-D-13-01447, DOI: 10.1371/journal.pcbi.1003677, ISSN: 1553-7358.

Erwin GD, Oksenberg N, Truty RM, Kostka D, Murphy KK, Ahituv N, Pollard KS, Capra JA. Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput. Biol. 2014 Jun; 10(6): e1003677. PMID: 24967590, PMCID: PMC4072507, PII: PCOMPBIOL-D-13-01447, DOI: 10.1371/journal.pcbi.1003677, ISSN: 1553-7358.

Sabouri N, Capra JA, Zakian VA. The essential Schizosaccharomyces pombe Pfh1 DNA helicase promotes fork movement past G-quadruplex motifs to prevent DNA damage. BMC Biol. 2014; 12: 101. PMID: 25471935, PMCID: PMC4275981, PII: s12915-014-0101-5, DOI: 10.1186/s12915-014-0101-5, ISSN: 1741-7007.

Capra JA, Erwin GD, McKinsey G, Rubenstein JL, Pollard KS. Many human accelerated regions are developmental enhancers. Philos. Trans. R. Soc. Lond., B, Biol. Sci [electronic-print]. 2013 Dec 12/19/2013; 368(1632): 20130025. PMID: 24218637, PMCID: PMC3826498, PII: rstb.2013.0025, DOI: 10.1098/rstb.2013.0025, ISSN: 1471-2970.

Schröder S, Herker E, Itzen F, He D, Thomas S, Gilchrist DA, Kaehlcke K, Cho S, Pollard KS, Capra JA, Schnölzer M, Cole PA, Geyer M, Bruneau BG, Adelman K, Ott M. Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells. Mol. Cell. 2013 Nov 11/7/2013; 52(3): 314-24. PMID: 24207025, PMCID: PMC3936344, PII: S1097-2765(13)00751-X, DOI: 10.1016/j.molcel.2013.10.009, ISSN: 1097-4164.

Capra JA, Stolzer M, Durand D, Pollard KS. How old is my gene?. Trends Genet [print-electronic]. 2013 Nov; 29(11): 659-68. PMID: 23915718, PMCID: PMC3812327, PII: S0168-9525(13)00111-X, DOI: 10.1016/j.tig.2013.07.001, ISSN: 0168-9525.

Capra JA, Stolzer M, Durand D, Pollard KS. How old is my gene?. Trends Genet [print-electronic]. 2013 Nov; 29(11): 659-68. PMID: 23915718, PMCID: PMC3812327, PII: S0168-9525(13)00111-X, DOI: 10.1016/j.tig.2013.07.001, ISSN: 0168-9525.

Capra JA, Hubisz MJ, Kostka D, Pollard KS, Siepel A. A model-based analysis of GC-biased gene conversion in the human and chimpanzee genomes. PLoS Genet [print-electronic]. 2013; 9(8): e1003684. PMID: 23966869, PMCID: PMC3744432, PII: PGENETICS-D-13-00656, DOI: 10.1371/journal.pgen.1003684, ISSN: 1553-7404.

Wamstad JA, Alexander JM, Truty RM, Shrikumar A, Li F, Eilertson KE, Ding H, Wylie JN, Pico AR, Capra JA, Erwin G, Kattman SJ, Keller GM, Srivastava D, Levine SS, Pollard KS, Holloway AK, Boyer LA, Bruneau BG. Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell [print-electronic]. 2012 Sep 9/28/2012; 151(1): 206-20. PMID: 22981692, PMCID: PMC3462286, PII: S0092-8674(12)01062-8, DOI: 10.1016/j.cell.2012.07.035, ISSN: 1097-4172.

Capra JA, Williams AG, Pollard KS. ProteinHistorian: tools for the comparative analysis of eukaryote protein origin. PLoS Comput. Biol [print-electronic]. 2012; 8(6): e1002567. PMID: 22761559, PMCID: PMC3386163, PII: PCOMPBIOL-D-11-01559, DOI: 10.1371/journal.pcbi.1002567, ISSN: 1553-7358.

Hirschey MD, Shimazu T, Capra JA, Pollard KS, Verdin E. SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2. Aging (Albany NY). 2011 Jun; 3(6): 635-42. PMID: 21701047, PMCID: PMC3164371, PII: 100339, ISSN: 1945-4589.

Paeschke K, Capra JA, Zakian VA. DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase. Cell. 2011 May 5/27/2011; 145(5): 678-91. PMID: 21620135, PMCID: PMC3129610, PII: S0092-8674(11)00437-5, DOI: 10.1016/j.cell.2011.04.015, ISSN: 1097-4172.

Katzman S, Capra JA, Haussler D, Pollard KS. Ongoing GC-biased evolution is widespread in the human genome and enriched near recombination hot spots. Genome Biol Evol [print-electronic]. 2011; 3: 614-26. PMID: 21697099, PMCID: PMC3157837, PII: evr058, DOI: 10.1093/gbe/evr058, ISSN: 1759-6653.

Capra JA, Pollard KS. Substitution patterns are GC-biased in divergent sequences across the metazoans. Genome Biol Evol [print-electronic]. 2011; 3: 516-27. PMID: 21670083, PMCID: PMC3138425, PII: evr051, DOI: 10.1093/gbe/evr051, ISSN: 1759-6653.

Capra JA, Pollard KS, Singh M. Novel genes exhibit distinct patterns of function acquisition and network integration. Genome Biol [print-electronic]. 2010; 11(12): R127. PMID: 21187012, PMCID: PMC3046487, PII: gb-2010-11-12-r127, DOI: 10.1186/gb-2010-11-12-r127, ISSN: 1474-760X.

Capra JA, Paeschke K, Singh M, Zakian VA. G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae. PLoS Comput. Biol. 2010; 6(7): e1000861. PMID: 20676380, PMCID: PMC2908698, DOI: 10.1371/journal.pcbi.1000861, ISSN: 1553-7358.

Capra JA, Carbone L, Riesenfeld SJ, Wall JD. Genomics through the lens of next-generation sequencing. Genome Biol [print-electronic]. 2010; 11(6): 306. PMID: 20587080, PMCID: PMC2911104, PII: gb-2010-11-6-306, DOI: 10.1186/gb-2010-11-6-306, ISSN: 1474-760X.

Capra JA, Laskowski RA, Thornton JM, Singh M, Funkhouser TA. Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure. PLoS Comput. Biol [print-electronic]. 2009 Dec; 5(12): e1000585. PMID: 19997483, PMCID: PMC2777313, DOI: 10.1371/journal.pcbi.1000585, ISSN: 1553-7358.

Capra JA, Singh M. Characterization and prediction of residues determining protein functional specificity. Bioinformatics [print-electronic]. 2008 Jul 7/1/2008; 24(13): 1473-80. PMID: 18450811, PMCID: PMC2718669, PII: btn214, DOI: 10.1093/bioinformatics/btn214, ISSN: 1367-4811.

Capra JA, Singh M. Predicting functionally important residues from sequence conservation. Bioinformatics [print-electronic]. 2007 Aug 8/1/2007; 23(15): 1875-82. PMID: 17519246, PII: btm270, DOI: 10.1093/bioinformatics/btm270, ISSN: 1367-4811.

Rosen GD, La Porte NT, Diechtiareff B, Pung CJ, Nissanov J, Gustafson C, Bertrand L, Gefen S, Fan Y, Tretiak OJ, Manly KF, Park MR, Williams AG, Connolly MT, Capra JA, Williams RW. Informatics center for mouse genomics: the dissection of complex traits of the nervous system. Neuroinformatics. 2003; 1(4): 327-42. PMID: 15043219, PII: NI:1:4:327, DOI: 10.1385/NI:1:4:327, ISSN: 1539-2791.