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Adam Siepel

Adam Siepel

Professor
Cancer Center Member

Ph.D., University of California, Santa Cruz, 2005

asiepel@cshl.edu | 516-367-6922

Siepel Lab Website   Faculty Profile

I am a computer scientist who is fascinated by the challenge of making sense of vast quantities of genetic data. My research group focuses in particular on questions involving molecular evolution and transcriptional regulation, with applications to cancer and other diseases as well as to plant breeding and agriculture.

Modern genomic technologies make it relatively easy to generate rich data sets describing genome sequences, RNA expression, chromatin states, and many other aspects of the storage, transmission, and expression of genetic information. For many problems in genetics today, the limiting step is no longer in data generation, but in integrating, interpreting, and understanding the available data. Addressing these challenges requires expertise both in the practical arts of data analysis and in the theoretical underpinnings of statistics, computer science, and genetics.

My group focuses on a diverse collection of research questions in this interdisciplinary area, spanning applications in cancer biology, basic molecular biology, evolutionary genetics, infectious diseases, and agriculture. Over the years, our research has touched on topics including the identification of recombinant strains of HIV, the discovery of new human genes, the characterization of conserved regulatory elements in mammalian genomes, the identification of noncoding mutations important in cancer, and the discovery of ancient gene flow from humans to Neandertals. A general theme in our work is the development of precise mathematical models for the complex processes by which genomes evolve over time, and the use of 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. We collaborate closely with experimentalists in cancer biology, transcriptional regulation, plant breeding and many other areas.

John Simon Guggenheim Memorial Foundation Fellowship, 2012-2013
Alfred P. Sloan Foundation Research Fellowship, 2009-2011
David & Lucile Packard Foundation Fellowship for Science and Engineering, 2007
Microsoft Research Faculty Fellowship Program, 2007
National Science Foundation (NSF) CAREER Award, 2007

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All Publications

A humanized NOVA1 splicing factor alters mouse vocal communications

18 Feb 2025 | Nature Communications | 16(1):1542
Tajima, Yoko;  Vargas, César;  Ito, Keiichi;  Wang, Wei;  Luo, Ji-Dung;  Xing, Jiawei;  Kuru, Nurdan;  Machado, Luiz;  Siepel, Adam;  Carroll, Thomas;  Jarvis, Erich;  Darnell, Robert;  

Probabilistic and machine-learning methods for predicting local rates of transcription elongation from nascent RNA sequencing data

8 Feb 2025 | Nucleic Acids Research (NAR) | 53(4)
Liu, Lingjie;  Zhao, Yixin;  Hassett, Rebecca;  Toneyan, Shushan;  Koo, Peter;  Siepel, Adam;  

Probabilistic and machine-learning methods for predicting local rates of transcription elongation from nascent RNA sequencing data.

8 Feb 2025 | Nucleic Acids Research (NAR) | 53(4)
Liu, Lingjie;  Zhao, Yixin;  Hassett, Rebecca;  Toneyan, Shushan;  Koo, Peter;  Siepel, Adam;  

Extensive genome evolution distinguishes maize within a stable tribe of grasses

24 Jan 2025 | bioRxiv
Stitzer, Michelle;  Seetharam, Arun;  Scheben, Armin;  Hsu, Sheng-Kai;  Schulz, Aimee;  AuBuchon-Elder, Taylor;  El-Walid, Mohamed;  Ferebee, Taylor;  Hale, Charles;  La, Thuy;  Liu, Zong-Yan;  McMorrow, Sarah;  Minx, Patrick;  Phillips, Alyssa;  Syring, Michael;  Wrightsman, Travis;  Zhai, Jingjing;  Pasquet, Rémy;  McAllister, Christine;  Malcomber, Simon;  Traiperm, Paweena;  Layton, Daniel;  Zhong, Jinshun;  Costich, Denise;  Dawe, R;  Fengler, Kevin;  Harris, Charlotte;  Irelan, Zach;  Llaca, Victor;  Parakkal, Praveena;  Zastrow-Hayes, Gina;  Woodhouse, Margaret;  Cannon, Ethalinda;  Portwood, John;  Andorf, Carson;  Albert, Patrice;  Birchler, James;  Siepel, Adam;  Ross-Ibarra, Jeffrey;  Romay, M;  Kellogg, Elizabeth;  Buckler, Edward;  Hufford, Matthew;  

Teosinte Pollen Drive guides maize diversification and domestication by RNAi

7 Aug 2024 | Nature
Berube, Benjamin;  Ernst, Evan;  Cahn, Jonathan;  Roche, Benjamin;  de Santis Alves, Cristiane;  Lynn, Jason;  Scheben, Armin;  Grimanelli, Daniel;  Siepel, Adam;  Ross-Ibarra, Jeffrey;  Kermicle, Jerry;  Martienssen, Robert;  

Inferring polygenic negative selection underlying an individual trait as a distribution of fitness effects (DFEs) from GWAS summary statistics

2024 | bioRxiv
Xue, Alexander;  Huang, Yi-Fei;  Siepel, Adam;  

Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer

5 Jul 2024 | Cancer Discovery
Serio, Ryan;  Scheben, Armin;  Lu, Billy;  Gargiulo, Domenic;  Patruno, Lucrezia;  Buckholtz, Caroline;  Chaffee, Ryan;  Jibilian, Megan;  Persaud, Steven;  Staklinski, Stephen;  Hassett, Rebecca;  Brault, Lise;  Ramazzotti, Daniele;  Barbieri, Christopher;  Siepel, Adam;  Nowak, Dawid;  

Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones

30 Jan 2024 | Journal of Mammary Gland Biology and Neoplasia | 29(1):3
Ortiz, Jenelys;  Lewis, Steven;  Ciccone, Michael;  Chatterjee, Deeptiman;  Henry, Samantha;  Siepel, Adam;  Dos Santos, Camila;  

DNA-sequence and epigenomic determinants of local rates of transcription elongation

23 Dec 2023 | bioRxiv
Liu, Lingjie;  Zhao, Yixin;  Siepel, Adam;  

Identification of constrained sequence elements across 239 primate genomes

29 Nov 2023 | Nature
Kuderna, Lukas;  Ulirsch, Jacob;  Rashid, Sabrina;  Ameen, Mohamed;  Sundaram, Laksshman;  Hickey, Glenn;  Cox, Anthony;  Gao, Hong;  Kumar, Arvind;  Aguet, Francois;  Christmas, Matthew;  Clawson, Hiram;  Haeussler, Maximilian;  Janiak, Mareike;  Kuhlwilm, Martin;  Orkin, Joseph;  Bataillon, Thomas;  Manu, Shivakumara;  Valenzuela, Alejandro;  Bergman, Juraj;  Rouselle, Marjolaine;  Silva, Felipe;  Agueda, Lidia;  Blanc, Julie;  Gut, Marta;  de Vries, Dorien;  Goodhead, Ian;  Harris, R;  Raveendran, Muthuswamy;  Jensen, Axel;  Chuma, Idriss;  Horvath, Julie;  Hvilsom, Christina;  Juan, David;  Frandsen, Peter;  Schraiber, Joshua;  de Melo, Fabiano;  Bertuol, Fabrício;  Byrne, Hazel;  Sampaio, Iracilda;  Farias, Izeni;  Valsecchi, João;  Messias, Malu;  da Silva, Maria;  Trivedi, Mihir;  Rossi, Rogerio;  Hrbek, Tomas;  Andriaholinirina, Nicole;  Rabarivola, Clément;  Zaramody, Alphonse;  Jolly, Clifford;  Phillips-Conroy, Jane;  Wilkerson, Gregory;  Abee, Christian;  Simmons, Joe;  Fernandez-Duque, Eduardo;  Kanthaswamy, Sree;  Shiferaw, Fekadu;  Wu, Dongdong;  Zhou, Long;  Shao, Yong;  Zhang, Guojie;  Keyyu, Julius;  Knauf, Sascha;  Le, Minh;  Lizano, Esther;  Merker, Stefan;  Navarro, Arcadi;  Nadler, Tilo;  Khor, Chiea;  Lee, Jessica;  Tan, Patrick;  Lim, Weng;  Kitchener, Andrew;  Zinner, Dietmar;  Gut, Ivo;  Melin, Amanda;  Guschanski, Katerina;  Schierup, Mikkel;  Beck, Robin;  Karakikes, Ioannis;  Wang, Kevin;  Umapathy, Govindhaswamy;  Roos, Christian;  Boubli, Jean;  Siepel, Adam;  Kundaje, Anshul;  Paten, Benedict;  Lindblad-Toh, Kerstin;  Rogers, Jeffrey;  Marques Bonet, Tomas;  Farh, Kyle;  

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