Principal Investigator

Awardee Organization

Mayo Clinic Rochester
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Detection of somatic, subclonal and mosaic CNVs from sequencing

Progress in technology has made individual genome sequencing a clinical reality, with partial genome sequencing already in use in clinical care. In fact, it is expected that within a few years whole genome sequencing will be a standard procedure that will allow discovering personal genomic variants of all types and thus greatly facilitate individualized medicine. However, fast and reliable analysis of such data is challenging; and improvements in analytics are needed before the clinical potential of whole genome sequencing can be realized. Specifically, copy number variations account for a large proportion of human genetic diversity, are frequently observed in cancer, and have been associated with multiple diseases, cancer susceptibility, cancer progression and invasiveness, individual response to treatment, and patients' quality of life after treatment (i.e., emergence of side effects). Therefore, comprehensive identification and analysis of copy-number variants will help us more fully elucidate the biology of their functional effects on human health (in particular, for cancer emergence and progression) and will facilitate clinical diagnostics and treatment. However, abilities to detect CNVs/CNAs from sequencing are not fully utilized due to immature analytical approaches. This proposal suggests continuing development and enhancement of analytical approaches for the detection of copy number variants and aberrations from sequencing data. Historically, the development of concepts, techniques, and methods in the basic sciences has been followed by their transition and use in applied areas. Specifically, advances in biology lead to applications in medicine. The developments we propose anticipate many forthcoming applications of whole genome sequencing in medicine, and set up a computational framework to power clinical care with tools for copy number variants discovery and analysis.   3


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  • Zhou B, Ho SS, Greer SU, Spies N, Bell JM, Zhang X, Zhu X, Arthur JG, Byeon S, Pattni R, Saha I, Huang Y, Song G, Perrin D, Wong WH, Ji HP, Abyzov A, Urban AE. Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2. Nucleic acids research. 2019 May 7;47(8):3846-3861. PMID: 30864654
  • Zhou B, Ho SS, Greer SU, Zhu X, Bell JM, Arthur JG, Spies N, Zhang X, Byeon S, Pattni R, Ben-Efraim N, Haney MS, Haraksingh RR, Song G, Ji HP, Perrin D, Wong WH, Abyzov A, Urban AE. Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562. Genome research. 2019 Mar;29(3):472-484. Epub 2019 Feb 8. PMID: 30737237
  • Yanchus C, Drucker KL, Kollmeyer TM, Tsai R, Winick-Ng W, Liang M, Malik A, Pawling J, De Lorenzo SB, Ali A, Decker PA, Kosel ML, Panda A, Al-Zahrani KN, Jiang L, Browning JWL, Lowden C, Geuenich M, Hernandez JJ, Gosio JT, Ahmed M, Loganathan SK, Berman J, Trcka D, Michealraj KA, Fortin J, Carson B, Hollingsworth EW, Jacinto S, Mazrooei P, Zhou L, Elia A, Lupien M, He HH, Murphy DJ, Wang L, Abyzov A, Dennis JW, Maass PG, Campbell K, Wilson MD, Lachance DH, Wrensch M, Wiencke J, Mak T, Pennacchio LA, Dickel DE, Visel A, Wrana J, Taylor MD, Zadeh G, Dirks P, Eckel-Passow JE, Attisano L, Pombo A, Ida CM, Kvon EZ, Jenkins RB, Schramek D. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science (New York, N.Y.). 2022 Oct 7;378(6615):68-78. Epub 2022 Oct 6. PMID: 36201590
  • Panda A, Suvakov M, Mariani J, Drucker KL, Park Y, Jang Y, Kollmeyer TM, Sarkar G, Bae T, Kim JJ, Yoon WH, Jenkins RB, Vaccarino FM, Abyzov A. Clonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic. The CRISPR journal. 2023 Apr;6(2):176-182. PMID: 37071670
  • Sarangi V, Jang Y, Suvakov M, Bae T, Fasching L, Sekar S, Tomasini L, Mariani J, Vaccarino FM, Abyzov A. All2: A tool for selecting mosaic mutations from comprehensive multi-cell comparisons. PLoS computational biology. 2022 Apr 20;18(4):e1009487. doi: 10.1371/journal.pcbi.1009487. eCollection 2022 Apr. PMID: 35442945