Adam C. Siepel (born 1972) is an American computational biologist known for his research in comparative genomics and population genetics, particularly the development of statistical methods and software tools for identifying evolutionarily conserved sequences.[1][2][3][4] Siepel is currently Chair of the Simons Center for Quantitative Biology and Professor in the Watson School for Biological Sciences at Cold Spring Harbor Laboratory.[5]

Adam Siepel
Adam Siepel head shot.tiff
Adam C. Siepel

(1972-06-24) June 24, 1972 (age 46)
NationalityUnited States
Alma mater
Known forevolutionarily conserved sequences
Scientific career
ThesisComparative mammalian genomics: Models of evolution and detection of functional elements (2005)
Doctoral advisorDavid Haussler


Education and careerEdit

Siepel completed a B.S. in Agricultural and Biological Engineering at Cornell University in 1994, then worked at Los Alamos National Laboratory until 1996. From 1996 to 2001, he worked as a software developer at the National Center for Genome Resources in Santa Fe, while completing an M.S. in Computer Science at the University of New Mexico. He obtained a Ph.D. in Computer Science from the University of California, Santa Cruz in 2005. He was on the faculty of Cornell University from 2006 to 2014 and moved to Cold Spring Harbor Laboratory in 2014.


Siepel has worked on various problems at the intersection of computer science, statistics, evolutionary biology, and genomics. At Los Alamos National Laboratory, he developed phylogenetic methods for detecting recombinant strains of HIV,[6] and at the National Center for Genome Resources, he led the development of ISYS, a technology for integrating heterogeneous bioinformatics databases, analysis tools, and visualization programs.[7] Siepel also did theoretical work on algorithms for phylogeny reconstruction based on genome rearrangements, working with Bernard Moret at the University of New Mexico.[8] When Siepel left software development to join David Haussler's laboratory at the University of California, Santa Cruz, he turned to computational problems in comparative genomics. In Haussler's group, he developed several analysis methods based on phylogenetic hidden Markov models, including a widely used program called phastCons for identifying evolutionarily conserved sequences in genomic sequences.[9]

At Cornell, Siepel's research group continued to work on the identification and characterization of conserved non-coding sequences. They also studied fast-evolving sequences in both coding[10] and noncoding[11] regions, including human accelerated regions. In recent years, the Siepel laboratory has increasingly focused on human population genetics, developing methods for estimating the times in early human history when major population groups first diverged,[12] for measuring the influence of natural selection on transcription factor binding sites,[13] and for estimating probabilities that mutations across the human genome will have fitness consequences.[14] The group also has an active research program in transcriptional regulation, carried out in close collaboration with John T. Lis's laboratory.

A common theme in Siepel's research is the development of precise mathematical models for the complex processes by which genomes evolve over time. His research group uses these models, together with techniques from computer science and statistics, both to peer into the past, and to address questions of practical importance for human health.[15]

Awards and honoursEdit


  1. ^ a b Adam C. Siepel publications indexed by Google Scholar
  2. ^ Adam C. Siepel's publications indexed by the Scopus bibliographic database. (subscription required)
  3. ^ Brian Couger, M.; Pipes, L.; Squina, F.; Prade, R.; Siepel, A.; Palermo, R.; Katze, M. G.; Mason, C. E.; Blood, P. D. (2014). "Enabling large-scale next-generation sequence assembly with Blacklight". Concurrency and Computation: Practice and Experience. 26 (13): 2157–2166. doi:10.1002/cpe.3231. PMC 4185199.
  4. ^ ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET et al. (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature. 447 (7146): 799–816. Bibcode:2007Natur.447..799B. doi:10.1038/nature05874. PMC 2212820. PMID 17571346.CS1 maint: Uses authors parameter (link)
  5. ^ Adam Siepel's CV.
  6. ^ Siepel, A. C.; Halpern, A. L.; MacKen, C; Korber, B. T. (1995). "A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences". AIDS Research and Human Retroviruses. 11 (11): 1413–6. doi:10.1089/aid.1995.11.1413. PMID 8573400.
  7. ^ Siepel, A.; Farmer, A.; Tolopko, A.; Zhuang, M.; Mendes, P.; Beavis, W.; Sobral, B. (2001). "ISYS: A decentralized, component-based approach to the integration of heterogeneous bioinformatics resources". Bioinformatics. 17 (1): 83–94. doi:10.1093/bioinformatics/17.1.83. PMID 11222265.
  8. ^ Siepel, A. C. (2003). "An algorithm to enumerate sorting reversals for signed permutations". Journal of Computational Biology. 10 (3–4): 575–97. doi:10.1089/10665270360688200. PMID 12935346.
  9. ^ Siepel, A.; Bejerano, G; Pedersen, J. S.; Hinrichs, A. S.; Hou, M; Rosenbloom, K; Clawson, H; Spieth, J; Hillier, L. W.; Richards, S; Weinstock, G. M.; Wilson, R. K.; Gibbs, R. A.; Kent, W. J.; Miller, W; Haussler, D (2005). "Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes". Genome Research. 15 (8): 1034–50. doi:10.1101/gr.3715005. PMC 1182216. PMID 16024819.
  10. ^ Kosiol, C.; Vinař, T. Š.; Da Fonseca, R. R.; Hubisz, M. J.; Bustamante, C. D.; Nielsen, R.; Siepel, A. (2008). "Patterns of Positive Selection in Six Mammalian Genomes". PLoS Genetics. 4 (8): e1000144. doi:10.1371/journal.pgen.1000144. PMC 2483296. PMID 18670650.
  11. ^ Pollard, K. S.; Hubisz, M. J.; Rosenbloom, K. R.; Siepel, A. (2009). "Detection of nonneutral substitution rates on mammalian phylogenies". Genome Research. 20 (1): 110–21. doi:10.1101/gr.097857.109. PMC 2798823. PMID 19858363.
  12. ^ Gronau, I.; Hubisz, M. J.; Gulko, B.; Danko, C. G.; Siepel, A. (2011). "Bayesian inference of ancient human demography from individual genome sequences". Nature Genetics. 43 (10): 1031–4. doi:10.1038/ng.937. PMC 3245873. PMID 21926973.
  13. ^ Arbiza, L.; Gronau, I.; Aksoy, B. A.; Hubisz, M. J.; Gulko, B.; Keinan, A.; Siepel, A. (2013). "Genome-wide inference of natural selection on human transcription factor binding sites". Nature Genetics. 45 (7): 723–729. doi:10.1038/ng.2658. PMC 3932982. PMID 23749186.
  14. ^ Gulko, B.; Hubisz, M. J.; Gronau, I.; Siepel, A. (2015). "A method for calculating probabilities of fitness consequences for point mutations across the human genome". Nature Genetics. 47 (3): 276–283. doi:10.1038/ng.3196. PMC 4342276. PMID 25599402.
  15. ^ a b Guggenheim profile. Archived April 18, 2012, at the Wayback Machine