Machine Learning Computational Scientist

Email:****.****@*****.***

Mobile:+1-516-***-****

*** * *** **, ********, NY 11211

Ravi Sachidanandam

Executive Summary

* Bioinformatics: Pipelines on local/cloud servers. R, Shiny, Python, C, Perl, PHP, MySQL, Apache/Nginx, and Linux.

* Genomics: Algorithms, Genome databases, NGS analysis, Machine Learning (ML) applications, web-based tools

* NGS Core facilities: Created and expanded sequencing/bioinformatics cores at two academic centers

* NGS Technology development: Three granted US patents for sample preparation (small RNA, mtDNA, TCR repertoire)

* TCR immune repertoires: Invented experimental/analytical techniques for immune repertoires from mammals

* Publications: Genomics, Genetics, SNPs, small RNAs, mtDNA, virology, innate immunity, TCR repertoires.

* Leadership: Assembled software/wet-bench teams for multi-center as well as small, single lab projects

* Mentoring: Trained Masters/Ph.D students, technicians, and research assistants

* Education: Created courses in Bioinformatics, Computing, Statistics and Machine Learning.

* Startup experience: Co-founder, grew collaborations and business for startup, Girihlet Inc. Work Experience

Girihlet Inc. Oakland, CA. CSO/co-founder, (2018-present) Set the Scientific direction of company. Hired and developed teams for analytic and experimental work. Developed Computational pipelines and analysis. Developed Technology for NGS for TCR repertoire sequencing. Maintained collaborations with companies and research centers. Customer Acquisition. Published Scientific articles. Evaluated technologies for the laboratory. Maintained computational hardware and software. Managed databases and data backups.

NYU Tandon school of engineering, NY. Adjunct Faculty, (2019-2023) Helped design curriculum for the master's program in Bioinformatics. Developed course on advanced Biostatistics. Taught the course online every other semester

Mount Sinai School of Medicine, NY. Assistant Professor. (2008-2021) Established and directed the NGS core. Hired and managed team for analytical and experimental work. R&D for sequencing. Developed research program in genetics, mtDNA genetics, and TCR repertoire. Studied innate immunity and virology. Developed collaborations with diverse groups. Developed algorithms and software tools. Developed clinically relevant research programs. Collaborated with clinicians to apply NGS. Published scientific papers and reports. Taught and trained Ph.D students, technicians and research assistants Cold Spring Harbor Laboratory, NY. Senior Computer Scientist. (1999-2008) Managed data coordination center for the human SNP project. Developed Bioinformatics software. Conducted research in Genomics and Bioinformatics. Trained research assistants. Published scientific papers and reports. Established and ran the cancer center bioinformatics core. Education & Qualifications

Ph.D. in Physics, University of Pennsylvania, Philadelphia, PA B. Tech. in Engineering Physics Indian Institute of Technology, Bombay, India Postdoctoral Fellow in Physics, Tel-Aviv University, Tel-Aviv, Israel Patents

US Patent number 10,920,220. Method for purifying T/B cell receptors (TCR/BCR) for sequencing US Patent number 9,868,946. Method of purifying mitochondrial DNA for NGS. US Patent number 9,487,825. Unbiased small RNA profiling, implemented in Perkin Elmer's NETFLEX small RNA kit. Publications/Projects (Select list)

Comprehensive list of publications (143)

T cell receptor (TCR) repertoires Tseek, our sensitive-and-specific method of profiling bulk T cell receptor repertoires, is free of biases and capable of discovering V, J segments. Tseek has been deployed in humans, mice, dogs, cats, pigs, and monkeys. Results have included establishment of the causative role of CD4 T cells in a colitis mouse model, the role of interferon-gamma in cancer immunotherapy, identification of NK T cell repertoires in pigs, characterisation of the human response to vaccines and establishment of properties of the TCR repertoires in dogs.

1. Clonal Deletion of Tumor-Specific T Cells by Interferon-$\gamma$ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade. Pai CS et al. Immunity. 2019 Feb 1. pii: S1074-7613(19)30029-9. PMID: 30737146 2. Diet Modifies Colonic Microbiota and CD4+ T-Cell Repertoire to Induce Flares of Colitis in Mice with Myeloid-Cell Expression of Interleukin 23. Chen L, He Z, Iuga AC, Martins Filho SN, Faith JJ, Clemente JC, Deshpande M, Jayaprakash A, Colombel JF, Lafaille JJ, Sachidanandam R, Furtado GC, Lira SA. Gastroenterology. 2018 Oct;155(4): 1177-1191.e16. PMID:29909020 3. Analysis of T cell antigen receptor expression by porcine natural killer T cells Guan Yang, Bianca Libanori Artiaga, Anitha Jayaprakash, Ravi Sachidanandam and John Driver. J Immunol May 1, 2018, 200 (1 Supplement) 59.16. PMID:30777925 4. The T cell receptor repertoire reflects the dynamics of the immune response to vaccination. Kevin Mohammed, Austin Meadows, Saboor Hekmaty, Sandra Hatem, Viviana Simon, Anitha D.Jayaprakash, Ravi Sachidanandam. BioRxiv 2021.12.09.471735 Innate immune response of Bats to Ebola and Marburg viruses Identified the characteristics of the innate immune responses of bats to Ebola and Marburg viruses which allows bats to survive infections and serve as reservoirs. We also identified a novel gamma herpesvirus that infects bat cells.

1. Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats. Anitha D Jayaprakash, Adam J Ronk, Abhishek N Prasad, Michael F Covington, Kathryn R Stein, Toni M Schwarz, Saboor Hekmaty, Karla A Fenton, Thomas W Geisbert, Christopher F Basler, Alexander Bukreyev, Ravi Sachidanandam. Viruses 2023 Jan 26;15(2):350. PMID:36851566 2. Innate Immune Responses of Bat and Human Cells to Filoviruses:Commonalities and Distinctions. Kuzmin IV, Schwarz TM, Ilinykh PA, Jordan I, Ksiazek TG, Sachidanandam R, Basler CF, Bukreyev A. J Virol. 2017 Mar 29;91(8):e02471-16. PMID:28122983 3. Isolation and Characterization of a Novel Gammaherpesvirus from a Microbat Cell Line. Shabman RS, Shrivastava S, Tsibane T, Attie O, Jayaprakash A, Mire CE, Dilley KE, Puri V, Stockwell TB, Geisbert TW, Sachidanandam R, Basler CF. mSphere. 2016 Feb 17;1(1):e00070- 15. PMID:27303702

Genomics I established the data center for the first large-scale map of human variation (SNPs). SpliceRack, a compendium of mRNA splice- sites in 5 model organisms (H. sapiens, M. musculus, D. melanogaster, C. elegans and A. thaliana) was created as a resource that was widely used by the community and helped identify novel indicators of splice-site strength. Kismeth, a tool for analysis of DNA methylation patterns in plants was created to address an unmet need in the plant community. 1. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Sachidanandam R et al. International SNP Map Working Group. Nature. 2001 Feb 15;409(6822):928-33. PMID:11237013 2. Comprehensive splice-site analysis using comparative genomics. Sheth N, Roca X, Hastings ML, Roeder T, Krainer AR, Sachidanandam R. Nucleic Acids Res. 2006;34(14):3955-67. PMID:16914448 3. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics. Roca X, Olson AJ, Rao AR, Enerly E, Kristensen VN, Børresen-Dale AL, Andresen BS, Krainer AR, Sachidanandam R. Genome Res. 2008 Jan;18(1):77-87. PMID:18032726 piRNAs and small RNAs We characterized piRNAs in the germline in several early, foundational papers in the field. My tools helped explain piRNA biogenesis as well as their roles in transposon control in the germline. We also designed shRNA libraries for genome-wide screens in mouse and human genomes. My first wet-bench project identified biases in the standard Tuschl protocol for small RNA sequencing, and invented a solution, which is implemented in the best-performing NextFlex small RNA sequencing toolkit from PerkinElmers. 1. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ. Cell. 2007 Mar23;128(6):1089-103. PMID:17346786 2. Miwi catalysis is required for piRNA amplification independent LINE1 transposon silencing. Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, Antony C, Sachidanandam R, Pillai RS. Nature. 2011 Nov 27;480(7376):264-7. PMID:22121019 3. Identification and remediation of biases in the activity of RNA ligases in small-RNA deep sequencing. Jayaprakash AD, Jabado O, Brown BD, Sachidanandam R. Nucleic Acids Res. 2011 Nov;39(21): e141. PMID:21890899 Mitochondrial genetics Invented Mseek to purify mtDNA. Discovered inter-cellular exchange of mtDNA. Carefully designed single cell experiments demonstrated this exchange and showed heteroplasmy is stable over generations. 1. Stable heteroplasmy at the single cell level is facilitated by inter-cellular exchange of mtDNA. Jayaprakash AD, Benson EK, Gone S, Liang, R Shim J, Lambertini L, Toloue MM, Wigler, M, Aaronson SA, Sachidanandam R. Nucleic Acids Res. 2015 Feb 4. PMID:25653158 Tools (Select list)

Comprehensive list of tools

Tvax: Shiny tool to explore TCR repertoire response to mRNA Covid vaccine. Filobat: Shiny tool to explore innate immune response to Ebola and Marburg. Kismeth: Bisulfite analysis of DNA methylation in plants. SpliceRack: mRNA splice sites in H. sapiens, M. musculus, D. melanogaster, C. elegans and A. thaliana. mitoviewer: Custom viewer for mtDNA variants.

Barcode Caddy: Multiplexing samples in a NGS instruments to minimize barcode cross-talk. Amplicon sequencing: Amplicon sequencing using NGS instead of Sanger JABseq: Just-in-time barcoding for NGS amplicon sequencing, barcoding done at run-time for flexibility in multiplexing si/shRNA designer: Tool for designing sh/si RNA silencing constructs. Abbey: ABI-file viewer for sanger sequencing data

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