Ratan, Aakrosh

Primary Appointment

Associate Professor, Genome Sciences, Public Health Sciences

Education

BTech, Electrical Engineering, Indian Institute of Technology
SM, Computer Science, National University of Singapore
PhD, Computer Science and Engineering, Pennsylvania State University, University Park, PA

Contact Information

MSB-6131F; West Complex, 1300 JPA
Center for Public Health Genomics
Charlottesville, VA 22908
Telephone: 434-982-6583
Fax: 434-982-1815
Email: ar7jq@virginia.edu

Research Disciplines

Bioinformatics and Genomics, Cancer Biology, Computational Biology, Genetics, Molecular Biology

Research Interests

Genomics, Molecular Evolution, Algorithm Design and Analysis

Research Description

1. Detection of genomic variation: I have developed several methods to identify and map variants (SNPs, indels, and large-scale rearrangements) from large-scale sequencing datasets. This includes identification and genotyping of variants in species with a haploid representation (reference genome), species with multiple representations (pangenome), as well as species where we lack a reference genome. Several of these methods utilize graphs as a framework to represent genome variation and sequence uncertainty.

a. Sirén J, Monlong J, Chang X, Novak AM, Eizenga JM, Markello C, Sibbesen JA, Hickey G, Chang P, Carroll A, Gupta N, Gabriel S, Blackwell, TW, Ratan A, Taylor KD, Rich SS, Rotter JI, Haussler D, Garrison E, Paten B. Pangenomics enables genotyping of known structural variants in 5202 diverse genomes. Science. 2022, 374(6574), p. abg8871. DOI: 10.1126/science.abg8871.

b. Kathuria K, Ratan A. SVXplorer: Three-tier approach to identification of structural variants via sequential recombination of discordant cluster signatures. PLoS Comput Biol. 2020 Mar;16(3):e1007737. PubMed PMID: 32182236; PubMed Central PMCID: PMC7100977.

c. Kedzierska KZ, Gerber L, Cagnazzi D, Krützen M, Ratan A*, Kistler L*. SONiCS: PCR stutter noise correction in genome-scale microsatellites. Bioinformatics. 2018 Dec 1;34(23):4115-4117. PubMed PMID: 29931218; PubMed Central PMCID: PMC6454461.

d. Kistler L, Johnson SM, Irwin MT, Louis EE, Ratan A*, Perry GH*. A massively parallel strategy for STR marker development, capture, and genotyping. Nucleic Acids Res. 2017 Sep 6;45(15):e142. PubMed PMID: 28666376; PubMed Central PMCID: PMC5587753.

2. Large-scale analyses of cancer genomic datasets: Tumor sequencing experiments can provide insight into the changes driving tumorigenesis and identify covariates that can affect clinical prognosis. I have developed several methods to analyze large cancer genomic datasets accounting for the observed heterogeneity and clinical covariates. I have also led or co-led several studies that have analyzed large-scale datasets to dissect the role of genomic variation in cancer. For example, in collaboration with Dr. Anindya Dutta at the University of Alabama, we published two studies and a review on the role of germline variation in the clinical outcome of cancer patients.

a. Sienkiewicz K, Chen J, Chatrath A, Lawson J, Sheffield N, Zhang L, Ratan A. Detecting molecular subtypes from multi-omics datasets using SUMO. Cell Reports Methods. 2022, 2(1):100152. DOI: 10.1016/j.crmeth.2021.100152
b. Chatrath A, Ratan A, Dutta. Germline variants predictive of tumor mutational burden and immune checkpoint inhibitor efficacy. iScience. 2021 24(3). PubMed PMID: 33786423; PubMed Central PMCID: PMC7988326.
c. Sienkiewicz K, Ratan A. Protocol for integrative subtyping of lower-grade gliomas using the SUMO pipeline. STAR Protocols. 2022;3(1):101110. DOI: 10.1016/j.xpro.2021.101110
d. Chatrath A, Przanowska R, Kiran S, Su Z, Saha S, Wilson B, Tsunematsu T, Ahn JH, Lee KY, Paulsen T, Sobierajska E, Kiran M, Tang X, Li T, Kumar P, Ratan A, Dutta A. The pan-cancer landscape of prognostic germline variants in 10,582 patients. Genome Med. 2020 Feb 17;12(1):15. PubMed PMID: 32066500; PubMed Central PMCID: PMC7027124.

3. Genomics of LGL Leukemia: Large Granular Lymphocyte (LGL) Leukemia is a rare lymphoproliferative disorder of CD8+ T or natural cell (NK) lineage. I lead the bioinformatics in a collaborative effort with Dr. Thomas Loughran at the UVA Cancer Center and Dr. Ross Hardison at Pennsylvania State University to assemble and analyze some of the largest cohorts of this rare disease. We recently published a manuscript focused on the mutational landscape of NK-LGL, and another manuscript that analyzed a large cohort of T-LGL patients is in press. I am also leading the integrative analysis of the various genetic and epigenetic datasets collected from LGL patients and those corresponding to the TEMRA cells, which are considered the normal counterparts of the leukemic LGL cells.

a. Cheon H, Xing JC, Moosic KB, Ung J, Chan V, Chung DS, Toro MF, Eighawy O, Wang JS, Hamele CE, Hardison RC, Olson TL, Tan S, Feith D, Ratan A, Loughran TP. Genomic Landscape of TCR Alpha-Beta and TCR Gamma-Delta T-Large Granular Lymphocyte Leukemia. Blood. 2022. DOI: 10.1182/blood.2021013164.
b. Olson TL, Cheon H, Xing JC, Olson KC, Paila U, Hamele CE, Neelamraju Y, Shemo BC, Schmachtenberg MW, Sundararaman SK, Toro MF, Keller CA, Farber EA, Onengut-Gumuscu S, Garrett-Bakelman FE, Hardison RC, Feith D, Ratan A, Loughran TP. Frequent somatic TET2 mutations in chronic NK-LGL leukemia with distinct patterns of cytopenias. Blood. 2021 Mar; PubMed PMID: 33786584
c. Moosic KB, Paila U, Olson KC, Dziewulska K, Wang TT, Xing JC, Ratan A, Feith DJ, Loughran TP, Olson TL. Genomics of LGL leukemia and select other rare leukemia/lymphomas. Best practice & research Clinical haematology. 2019 Sep;32(3):196–206. PubMed PMID: 31585620
d. Wang TT, Yang J, Dighe S, Schmachtenberg MW, Leigh NT, Farber E, Onengut-Gumuscu S, Feith DJ, Ratan A, Loughran TP, Olson TL. Whole Genome Sequencing of Spontaneously Occurring Rat Natural Killer Large Granular Lymphocyte Leukemia Identifies JAK1 Somatic Activating Mutation. Cancers 2020 12(1). PubMed PMID: 31947841; PubMed Central PMCID: PMC7017127.

4. Studies of genetic diversity: Genome-wide assessments of genetic diversity provide a powerful analytical tool that informs of the similarities, differences, origins, and evolutionary history of a species. I have applied both methods I have developed over the years and methods developed elsewhere to identify variants among and between members of several species. Using the observed allele frequencies, we have calculated metrics of population differentiation, such as the fixation index, and correlated them with phenotypes to identify adaptations and detect the causative mutations for a genetic trait or disease.

a. Wall JD, Ratan A, Stawiski E. Identification of African-Specific Admixture between Modern and Archaic Humans. Am J Hum Genet. 2019 Dec 5;105(6):1254-1261. PubMed PMID: 31809748; PubMed Central PMCID: PMC6904834.
b. Wall JD*, Stawiski EW*, Ratan A*, Kim HL*, Kim C*, Gupta R*, Suryamohan K, Gusareva ES, Purbojati RW, Bhangale T, Stepanov V, Kharkov V, Schröder MS, Ramprasad V, Tom J, Durinck S, Bei Q, Li J, Guillory J, Phalke S, Basu A, Stinson J, Nair S, Malaichamy S, Biswas NK, Chambers JC, Cheng KC, George JT, Khor SS, Kim J, Cho B, Menon R, Sattibabu T, Bassi A, Deshmukh M, Verma A, Gopalan V, Shin J, Pratapneni M, Santhosh S, Tokunaga K, Md-Zain BM, Chan KG, Parani M, Natarajan P, Hauser M, Allingham RR, Santiago-Turla C, Ghosh A, Gadde SGK, Fuchsberger C, Forer L, Schoenherr S, Sudoyo H, Lansing JS, Friedlaender J, Koki G, Cox MP, Hammer M, Karafet T, Ang KC, Mehdi SQ, Radha V, Mohan V, Majumder PP*, Seshagiri S*, Seo J*, Schuster SC*, Peterson AS*. The GenomeAsia 100K Project enables genetic discoveries across Asia. Nature. 2019 Dec;576(7785):106-111. PubMed PMID: 31802016; PubMed Central PMCID: PMC7054211.
c. Kitchen SA*, Ratan A*, Bedoya-Reina OC, Burhans R, Fogarty ND, Miller W, Baums IB. Genomic Variants Among Threatened Acropora Corals. G3 (Bethesda). 2019 May 7;9(5):1633-1646. PubMed PMID: 30914426; PubMed Central PMCID: PMC6505131.
d. Fry E, Kim SK, Chigurapti S, Mika KM, Ratan A, Dammermann A, Mitchell BJ, Miller W, Lynch VJ. Functional Architecture of Deleterious Genetic Variants in the Genome of a Wrangel Island Mammoth. Genome Biol Evol. 2020 Mar 1;12(3):48-58. PubMed PMID: 32031213; PubMed Central PMCID: PMC7094797.