Dr. Keith A. Crandall is the Founding Director of the Computational Biology Institute at The George Washington University, in addition to being a Professor in the Milken Institute School of Public Health and the Department of Biological Sciences.
My research program has three main aspects. The first and central component is work on the development and testing through computer simulation of methods for the analysis of DNA sequence data. We have developed methods for estimating gene genealogies, detecting recombination, detecting selection, and measuring genetic diversity and demographic events in the history of a population. We develop software to implement many of these methods and then develop software to test our methods and many others by comparison through computer simulation. Through comparison and tests of robustness to assumption violations, we can gain great insights into why particular methods perform well or poorly and then are in a good position to redevelop improved methodology.
The remaining two aspects of my research program deal with applications of the above methodologies in two fairly distinct arenas. The first is in molecular ecology, conservation biology, and systematics research. We have applied the methods developed and tested in our lab (and many others) to examine the populations genetics, historical demography, and molecular ecology of various species of freshwater crayfish. We have also examined the molecular systematics of a variety of organisms, from the origin of dogs to the origin of freshwater crayfishes.
The second focus of my empirical research is in the area of the evolution of infectious diseases. Here we have explored bacterial genetics, viral dynamics (especially, HIV and SARS-CoV-2), and microbiome research. Our main goal with these projects is to explore the population dynamics, evolutionary diversity and molecular evolution of infectious disease, particularly relative to the evolution of drug resistance and identification of clinical associates with disease progression, treatment, and health outcomes through the development and implementation of novel multi-omics data integration methods.
The research outlined in these three main areas in my lab has enjoyed a diversity of funding from the National Institutes of Health, the National Science Foundation, and private agencies such as the Alfred P. Sloan Foundation and the Pharmaceutical Manufacturers of America. My research program is solidly in the genomics and bioinformatics arenas and applying these insights into conservation management, human health, and biomedical applications.
EDUCATION
Dr. Crandall graduated from Kalamazoo College (1987) with a BA in Mathematics and Biology. He then earned an MA (1993) in Statistics from Washington University in St. Louis and a PhD (1993) in Biology and Biomedical Sciences from the Washington University School of Medicine. He then completed an Alfred P. Sloan Postdoctoral Fellowship in Molecular Evolution and a National Science Foundation Postdoctoral Fellowship at the University of Texas in Austin.
PUBLICATIONS
For a complete list of publications, please visit Dr. Crandall's GoogleScholar page.
BIOINFORMATICS
Odom AR, Faits T, Castro-Nallar E, Crandall KA, Johnson WE. Metagenomic profiling pipelines improve taxonomic classification for 16S amplicon sequencing data. Sci Rep. 2023 Aug 26;13(1):13957. doi: 10.1038/s41598-023-40799-x. PMID: 37633998; PMCID: PMC10460424.
Knyazev S, Chhugani K, Sarwal V, Ayyala R, Singh H, Karthikeyan S, Deshpande D, Baykal PI, Comarova Z, Lu A, Porozov Y, Vasylyeva TI, Wertheim JO, Tierney BT, Chiu CY, Sun R, Wu A, Abedalthagafi MS, Pak VM, Nagaraj SH, Smith AL, Skums P, Pasaniuc B, Komissarov A, Mason CE, Bortz E, Lemey P, Kondrashov F, Beerenwinkel N, Lam TT, Wu NC, Zelikovsky A, Knight R, Crandall KA, Mangul S. Unlocking capacities of genomics for the COVID-19 response and future pandemics. Nat Methods. 2022 Apr;19(4):374-380. doi: 10.1038/s41592-022-01444-z. PMID: 35396471; PMCID: PMC9467803.
Rahnavard A, Chatterjee S, Sayoldin B, Crandall KA, Tekola-Ayele F, Mallick H. Omics community detection using multi-resolution clustering. Bioinformatics. 2021 Oct 25;37(20):3588-3594. doi: 10.1093/bioinformatics/btab317. PMID: 33974004; PMCID: PMC8545346.
Gogate N, Lyman D, Bell A, Cauley E, Crandall KA, Joseph A, Kahsay R, Natale DA, Schriml LM, Sen S, Mazumder R. COVID-19 biomarkers and their overlap with comorbidities in a disease biomarker data model. Brief Bioinform. 2021 Nov 5;22(6):bbab191. doi: 10.1093/bib/bbab191. PMID: 34015823; PMCID: PMC8195003.
Bendall ML, Gibson KM, Steiner MC, Rentia U, Pérez-Losada M, Crandall KA. HAPHPIPE: Haplotype Reconstruction and Phylodynamics for Deep Sequencing of Intrahost Viral Populations. Mol Biol Evol. 2021 Apr 13;38(4):1677-1690. doi: 10.1093/molbev/msaa315. PMID: 33367849; PMCID: PMC8042772.
Spurr LF, Alomran N, Bousounis P, Reece-Stremtan D, Prashant NM, Liu H, Słowiński P, Li M, Zhang Q, Sein J, Asher G, Crandall KA, Tsaneva-Atanasova K, Horvath A. ReQTL: identifying correlations between expressed SNVs and gene expression using RNA-sequencing data. Bioinformatics. 2020 Mar 1;36(5):1351-1359. doi: 10.1093/bioinformatics/btz750. PMID: 31589315; PMCID: PMC7058180.
Bendall ML, de Mulder M, Iñiguez LP, Lecanda-Sánchez A, Pérez-Losada M, Ostrowski MA, Jones RB, Mulder LCF, Reyes-Terán G, Crandall KA, Ormsby CE, Nixon DF. Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression. PLoS Comput Biol. 2019 Sep 30;15(9):e1006453. doi: 10.1371/journal.pcbi.1006453. PMID: 31568525; PMCID: PMC6786656.
Hong C, Manimaran S, Shen Y, Perez-Rogers JF, Byrd AL, Castro-Nallar E, Crandall KA, Johnson WE. PathoScope 2.0: a complete computational framework for strain identification in environmental or clinical sequencing samples. Microbiome. 2014 Sep 5;2:33. doi: 10.1186/2049-2618-2-33. PMID: 25225611; PMCID: PMC4164323.
GENOMICS
Bernot JP, Avdeyev P, Zamyatin A, Dreyer N, Alexeev N, Pérez-Losada M, Crandall KA. Chromosome-level genome assembly, annotation, and phylogenomics of the gooseneck barnacle Pollicipes pollicipes. Gigascience. 2022 Mar 12;11:giac021. doi: 10.1093/gigascience/giac021. PMID: 35277961; PMCID: PMC8917513.
Lewin HA, Richards S, Lieberman Aiden E, Allende ML, Archibald JM, Bálint M, Barker KB, Baumgartner B, Belov K, Bertorelle G, Blaxter ML, Cai J, Caperello ND, Carlson K, Castilla-Rubio JC, Chaw SM, Chen L, Childers AK, Coddington JA, Conde DA, Corominas M, Crandall KA, Crawford AJ, DiPalma F, Durbin R, Ebenezer TE, Edwards SV, Fedrigo O, Flicek P, Formenti G, Gibbs RA, Gilbert MTP, Goldstein MM, Graves JM, Greely HT, Grigoriev IV, Hackett KJ, Hall N, Haussler D, Helgen KM, Hogg CJ, Isobe S, Jakobsen KS, Janke A, Jarvis ED, Johnson WE, Jones SJM, Karlsson EK, Kersey PJ, Kim JH, Kress WJ, Kuraku S, Lawniczak MKN, Leebens-Mack JH, Li X, Lindblad-Toh K, Liu X, Lopez JV, Marques-Bonet T, Mazard S, Mazet JAK, Mazzoni CJ, Myers EW, O'Neill RJ, Paez S, Park H, Robinson GE, Roquet C, Ryder OA, Sabir JSM, Shaffer HB, Shank TM, Sherkow JS, Soltis PS, Tang B, Tedersoo L, Uliano-Silva M, Wang K, Wei X, Wetzer R, Wilson JL, Xu X, Yang H, Yoder AD, Zhang G. The Earth BioGenome Project 2020: Starting the clock. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2115635118. doi: 10.1073/pnas.2115635118. PMID: 35042800; PMCID: PMC8795548.
Lawniczak MKN, Durbin R, Flicek P, Lindblad-Toh K, Wei X, Archibald JM, Baker WJ, Belov K, Blaxter ML, Marques Bonet T, Childers AK, Coddington JA, Crandall KA, Crawford AJ, Davey RP, Di Palma F, Fang Q, Haerty W, Hall N, Hoff KJ, Howe K, Jarvis ED, Johnson WE, Johnson RN, Kersey PJ, Liu X, Lopez JV, Myers EW, Pettersson OV, Phillippy AM, Poelchau MF, Pruitt KD, Rhie A, Castilla-Rubio JC, Sahu SK, Salmon NA, Soltis PS, Swarbreck D, Thibaud-Nissen F, Wang S, Wegrzyn JL, Zhang G, Zhang H, Lewin HA, Richards S. Standards recommendations for the Earth BioGenome Project. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2115639118. doi: 10.1073/pnas.2115639118. PMID: 35042802; PMCID: PMC8795494.
MICROBIOME
Pérez-Losada M, Crandall KA. Spatial diversity of the skin bacteriome. Front Microbiol. 2023 Sep 19;14:1257276. doi: 10.3389/fmicb.2023.1257276. PMID: 37795302; PMCID: PMC10546022.
Shumyatsky G, Burrell A, Chaney H, Sami I, Koumbourlis AC, Freishtat RJ, Crandall KA, Zemanick ET, Hahn A. Using metabolic potential within the airway microbiome as predictors of clinical state in persons with cystic fibrosis. Front Med (Lausanne). 2023 Jan 9;9:1082125. doi: 10.3389/fmed.2022.1082125. PMID: 36698799; PMCID: PMC9868313.
Bustamante JM, Dawson T, Loeffler C, Marfori Z, Marchesi JR, Mullish BH, Thompson CC, Crandall KA, Rahnavard A, Allegretti JR, Cummings BP. Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans. Nutrients. 2022 Dec 7;14(24):5200. doi: 10.3390/nu14245200. PMID: 36558359; PMCID: PMC9785599.
Xavier JB, Young VB, Skufca J, Ginty F, Testerman T, Pearson AT, Macklin P, Mitchell A, Shmulevich I, Xie L, Caporaso JG, Crandall KA, Simone NL, Godoy-Vitorino F, Griffin TJ, Whiteson KL, Gustafson HH, Slade DJ, Schmidt TM, Walther-Antonio MRS, Korem T, Webb-Robertson BM, Styczynski MP, Johnson WE, Jobin C, Ridlon JM, Koh AY, Yu M, Kelly L, Wargo JA. The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View. Trends Cancer. 2020 Mar;6(3):192-204. doi: 10.1016/j.trecan.2020.01.004. Epub 2020 Feb 7. PMID: 32101723; PMCID: PMC7098063.
HUMAN HEALTH
Kanholm T, Rentia U, Hadley M, Karlow JA, Cox OL, Diab N, Bendall ML, Dawson T, McDonald JI, Xie W, Crandall KA, Burns KH, Baylin SB, Easwaran H, Chiappinelli KB. Oncogenic Transformation Drives DNA Methylation Loss and Transcriptional Activation at Transposable Element Loci. Cancer Res. 2023 Aug 1;83(15):2584-2599. doi: 10.1158/0008-5472.CAN-22-3485. PMID: 37249603; PMCID: PMC10527578.
Dawson T, Rentia U, Sanford J, Cruchaga C, Kauwe JSK, Crandall KA. Locus specific endogenous retroviral expression associated with Alzheimer's disease. Front Aging Neurosci. 2023 Jul 6;15:1186470. doi: 10.3389/fnagi.2023.1186470. PMID: 37484691; PMCID: PMC10359044.
Sun X, Liu Z, Li Z, Zeng Z, Peng W, Zhu J, Zhao J, Zhu C, Zeng C, Stearrett N, Crandall KA, Bachali P, Grammer AC, Lipsky PE. Abnormalities in intron retention characterize patients with systemic lupus erythematosus. Sci Rep. 2023 Mar 29;13(1):5141. doi: 10.1038/s41598-023-31890-4. PMID: 36991079; PMCID: PMC10060252.
Kassaye SG, Grossman Z, Vengurlekar P, Chai W, Wallace M, Rhee SY, Meyer WA 3rd, Kaufman HW, Castel A, Jordan J, Crandall KA, Kang A, Kumar P, Katzenstein DA, Shafer RW, Maldarelli F. Insights into HIV-1 Transmission Dynamics Using Routinely Collected Data in the Mid-Atlantic United States. Viruses. 2022 Dec 25;15(1):68. doi: 10.3390/v15010068. PMID: 36680108; PMCID: PMC9863702.
NATURAL HISTORY
Sammy De Grave, Wim Decock, Stefanie Dekeyzer, Peter J F Davie, Charles H J M Fransen, Christopher B Boyko, Gary C B Poore, Enrique Macpherson, Shane T Ahyong, Keith A Crandall, Valentin de Mazancourt, Masayuki Osawa, Tin-Yam Chan, Peter K L Ng, Rafael Lemaitre, Sancia E T van der Meij, Sandro Santos, Benchmarking global biodiversity of decapod crustaceans (Crustacea: Decapoda), Journal of Crustacean Biology, Volume 43, Issue 3, September 2023, ruad042, https://doi.org/10.1093/jcbiol/ruad042
Bernot JP, Owen CL, Wolfe JM, Meland K, Olesen J, Crandall KA. Major Revisions in Pancrustacean Phylogeny and Evidence of Sensitivity to Taxon Sampling. Mol Biol Evol. 2023 Aug 3;40(8):msad175. doi: 10.1093/molbev/msad175. PMID: 37552897; PMCID: PMC10414812.
Benny K K Chan, Niklas Dreyer, Andy S Gale, Henrik Glenner, Christine Ewers-Saucedo, Marcos Pérez-Losada, Gregory A Kolbasov, Keith A Crandall, Jens T Høeg, The evolutionary diversity of barnacles, with an updated classification of fossil and living forms, Zoological Journal of the Linnean Society, Volume 193, Issue 3, November 2021, Pages 789–846, https://doi.org/10.1093/zoolinnean/zlaa160
TOP CITED
Posada D, Crandall KA. MODELTEST: testing the model of DNA substitution. Bioinformatics. 1998;14(9):817-8. doi: 10.1093/bioinformatics/14.9.817. PMID: 9918953. >23,000 citations.
Clement M, Posada D, Crandall KA. TCS: a computer program to estimate gene genealogies. Mol Ecol. 2000 Oct;9(10):1657-9. doi: 10.1046/j.1365-294x.2000.01020.x. PMID: 11050560. >10,000 citations.
Templeton AR, Crandall KA, Sing CF. A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping and DNA sequence data. III. Cladogram estimation. Genetics. 1992 Oct;132(2):619-33. doi: 10.1093/genetics/132.2.619. PMID: 1385266; PMCID: PMC1205162. >3,000 citations.
Crandall KA, Bininda-Emonds OR, Mace GM, Wayne RK. Considering evolutionary processes in conservation biology. Trends Ecol Evol. 2000 Jul;15(7):290-295. doi: 10.1016/s0169-5347(00)01876-0. PMID: 10856956. > 2,000 citations.