- Biomedical Sciences Graduate Program | Aakrosh Ratan

Aakrosh Ratan

Education

  • PhD, Pennsylvania State University, University Park, PA
  • SM, National University of Singapore
  • BTech, Indian Institute of Technology

Contact

Research Interest(s)

Genomics, Molecular Evolution, Algorithm Design and Analysis

Research Description

My research is focused on study of genome variation and genetic diversity, and its consequences on species health and survival. I am interested in local changes consisting of substitutions and small indels that alter a few base pairs, as well as large-scale changes that consist of larger indels, rearrangements and copy number variations. My efforts are concentrated in the following areas:

1. Identification of variants: We are developing methods to identify and map variants (SNPs, indels, and large-scale rearrangements) from large-scale sequencing datasets. This includes identification of variants in species with a haploid representation (reference genome), species with multiple representations, as well as species where we lack a reference genome.

2. Study of genetic diversity: Genome-wide assessments of genetic diversity provide a powerful analytical tool that informs of the similarities, differences, origins and the evolutionary history of a species. We apply methods developed in (1) to identify variants among and between members of several species. The observed allele frequencies are then used to calculate metrics of population differentiation such as the fixation index, and can be correlated with phenotypes to identify adaptations, or used to detect the causative mutations for a genetic trait.

3. Cancer Genomics: Tumor sequencing experiments can provide insight into the changes driving tumorigenesis. The current sequencing platforms provide (given adequate coverage of the genomes) the high level of sensitivity and accuracy required to properly characterize the differences between a tumor/normal pair. We use the methods developed in (1) to view the unique somatic mutations accrued by a tumor, and germline mutations in the matched normal tissue. We are currently applying our methods to understand how genomic changes contribute to the pathogenesis of the T-cell form of Large Granular Lymphocyte (LGL) leukemia in collaboration with the Loughran lab at University of Virginia.

Selected Publications

  • Bedoya-Reina O, Ratan A, Burhans R, Kim H, Giardine B, Riemer C, Li Q, Olson T, Loughran T, Vonholdt B, Perry G, Schuster S, Miller W. Galaxy tools to study genome diversity. GigaScience. 2014;2(1): 17. PMID: 24377391 | PMCID: PMC3877877
  • Perry G, Louis E, Ratan A, Bedoya-Reina O, Burhans R, Lei R, Johnson S, Schuster S, Miller W. Aye-aye population genomic analyses highlight an important center of endemism in northern Madagascar. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(15): 5823-8. PMID: 23530231 | PMCID: PMC3625347
  • Ratan A, Miller W, Guillory J, Stinson J, Seshagiri S, Schuster S. Comparison of sequencing platforms for single nucleotide variant calls in a human sample. PloS one. 2013;8(2): e55089. PMID: 23405114 | PMCID: PMC3566181
  • Giardine B, Riemer C, Burhans R, Ratan A, Miller W. Some phenotype association tools in Galaxy: looking for disease SNPs in a full genome. Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.]. 2012; Unit15.2. PMID: 22948727 | PMCID: PMC3548453
  • Gupta R, Ratan A, Rajesh C, Chen R, Kim H, Burhans R, Miller W, Santhosh S, Davuluri R, Butte A, Schuster S, Seshagiri S, Thomas G. Sequencing and analysis of a South Asian-Indian personal genome. BMC genomics. 2012;13 440. PMID: 22938532 | PMCID: PMC3534380
  • Miller W, Schuster S, Welch A, Ratan A, Bedoya-Reina O, Zhao F, Kim H, Burhans R, Drautz D, Wittekindt N, Tomsho L, Ibarra-Laclette E, Herrera-Estrella L, Peacock E, Farley S, Sage G, Rode K, Obbard M, Montiel R, Bachmann L, Ingólfsson O, Aars J, Mailund T, Wiig O, Talbot S, Lindqvist C. Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(36): E2382-90. PMID: 22826254 | PMCID: PMC3437856
  • Miller W, Hayes V, Ratan A, Petersen D, Wittekindt N, Miller J, Walenz B, Knight J, Qi J, Zhao F, Wang Q, Bedoya-Reina O, Katiyar N, Tomsho L, Kasson L, Hardie R, Woodbridge P, Tindall E, Bertelsen M, Dixon D, Pyecroft S, Helgen K, Lesk A, Pringle T, Patterson N, Zhang Y, Kreiss A, Woods G, Jones M, Schuster S. Genetic diversity and population structure of the endangered marsupial Sarcophilus harrisii (Tasmanian devil). Proceedings of the National Academy of Sciences of the United States of America. 2011;108(30): 12348-53. PMID: 21709235 | PMCID: PMC3145710
  • Perry G, Reeves D, Melsted P, Ratan A, Miller W, Michelini K, Louis E, Pritchard J, Mason C, Gilad Y. A genome sequence resource for the aye-aye (Daubentonia madagascariensis), a nocturnal lemur from Madagascar. Genome biology and evolution. 2011;4(2): 126-35. PMID: 22155688 | PMCID: PMC3273163
  • Lindqvist C, Schuster S, Sun Y, Talbot S, Qi J, Ratan A, Tomsho L, Kasson L, Zeyl E, Aars J, Miller W, Ingólfsson O, Bachmann L, Wiig O. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(11): 5053-7. PMID: 20194737 | PMCID: PMC2841953
  • Ratan A, Zhang Y, Hayes V, Schuster S, Miller W. Calling SNPs without a reference sequence. BMC bioinformatics. 2010;11 130. PMID: 20230626 | PMCID: PMC2851604
  • Schuster S, Miller W, Ratan A, Tomsho L, Giardine B, Kasson L, Harris R, Petersen D, Zhao F, Qi J, Alkan C, Kidd J, Sun Y, Drautz D, Bouffard P, Muzny D, Reid J, Nazareth L, Wang Q, Burhans R, Riemer C, Wittekindt N, Moorjani P, Tindall E, Danko C, Teo W, Buboltz A, Zhang Z, Ma Q, Oosthuysen A, Steenkamp A, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh B, Makova K, Nekrutenko A, Mardis E, Patterson N, Pringle T, Chiaromonte F, Mullikin J, Eichler E, Hardison R, Gibbs R, Harkins T, Hayes V. Complete Khoisan and Bantu genomes from southern Africa. Nature. 2010;463(7283): 943-7. PMID: 20164927 | PMCID: PMC3890430
  • Miller W, Drautz D, Janecka J, Lesk A, Ratan A, Tomsho L, Packard M, Zhang Y, McClellan L, Qi J, Zhao F, Gilbert M, Dalén L, Arsuaga J, Ericson P, Huson D, Helgen K, Murphy W, Götherström A, Schuster S. The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus). Genome research. 2009;19(2): 213-20. PMID: 19139089 | PMCID: PMC2652203
  • Willerslev E, Gilbert M, Binladen J, Ho S, Campos P, Ratan A, Tomsho L, da Fonseca R, Sher A, Kuznetsova T, Nowak-Kemp M, Roth T, Miller W, Schuster S. Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution. BMC evolutionary biology. 2009;9 95. PMID: 19432984 | PMCID: PMC2694787
  • Ma J, Ratan A, Raney B, Suh B, Miller W, Haussler D. The infinite sites model of genome evolution. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(38): 14254-61. PMID: 18787111 | PMCID: PMC2533685
  • Ma J, Ratan A, Raney B, Suh B, Zhang L, Miller W, Haussler D. DUPCAR: reconstructing contiguous ancestral regions with duplications. Journal of computational biology : a journal of computational molecular cell biology. 2008;15(8): 1007-27. PMID: 18774902 | PMCID: PMC3205822
  • Miller W, Drautz D, Ratan A, Pusey B, Qi J, Lesk A, Tomsho L, Packard M, Zhao F, Sher A, Tikhonov A, Raney B, Patterson N, Lindblad-Toh K, Lander E, Knight J, Irzyk G, Fredrikson K, Harkins T, Sheridan S, Pringle T, Schuster S. Sequencing the nuclear genome of the extinct woolly mammoth. Nature. 2008;456(7220): 387-90. PMID: 19020620