Clinical OMICS

JAN-FEB 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 34 of 51 January/February 2019 Clinical OMICs 33 in parallel." In addition, Tapestri could be used to identify clinically actionable rare cancer cells that come back after treatment in what is known as minimum residual disease. In a recently published proof-of-concept paper in Genome Research entitled, "High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics," Mission Bio researchers described how they sequenced longitudinally collected acute myeloid leukemia (AML) tumor populations from two patients and genotyped up to 62 disease-relevant loci across more than 16,000 indi- vidual cells. The researchers stated that "targeted single-cell sequencing was able to sensitively identify cells harbor- ing pathogenic mutations during complete remission and uncovered complex clonal evolution within AML tumors that was not observable with bulk sequencing." Based on these results, the researchers proposed that the ability to characterize genetic heterogeneity in tumor cell popula- tions "will make feasible the routine analysis of AML het- erogeneity, leading to improved stratification and therapy selection for the disease." The potential applications for the Tapestri platform are widespread, reaching areas outside of oncology. For example, Mission Bio recently joined the National Insti- tute of Standards and Technology (NIST) consortium for genome editing which "addresses the measurements and standards needed to increase confidence and lower the risk of utilizing genome-editing technologies in research and commercial products." In this role, Tapestri can perform single-cell analysis in the context of genome editing. It can identify if edits occurred in a homo- or heterozygous manner and if multi- ple edits have occurred in the same cell type. The informa- tion that is needed to avoid pitfalls in making gene editing safe for patients, for example, in the introduction of off-tar- get edits or DNA rearrangements, is now possible with the Tapestri platform. Determining the Response to Cancer Treatment Haluk Tezcan, M.D., CMO at Lexent Bio, said that "oncol- ogists are data driven." If Tezcan has his way, they will get the data they need from his company. Lexent, one of the newest companies in precision med- icine, will use a blood-only approach (no tissue biopsy needed) to follow cancer over a course of time by providing the methylation status of patients' cfDNA. Lexent's CEO Ken Nesmith said the company is "not focused on diagnosing disease." Rather, the company's "liquid biopsy technology will help oncologists and their patients understand if the patients are responding to treat- ment, sooner and more accurately than currently possible." To ensure that this information can be generated, the Lex- ent team makes a point of evaluating the best methods to map the cell-free methylome. In one study, company sci- entists compared bisulfite conversion of cfDNA followed by whole-genome bisulfite sequencing (WGBS) and bead-based fractionation of cfDNA followed by whole-genome sequenc- ing (WGS). In applying these two approaches to cfDNA from patients with advanced-stage cancer and healthy controls, the sci- entists found that methyl- ation differences in CpG islands and shores, but not differences in gene bodies or promoters, were effec- tive at segregating cancer samples from healthy samples. The scientists also found that WGBS was a more sensi- tive method to detect changes in hypomethylated regions. By analyzing the WGS and methylation status of cfDNA, Lexent hopes to provide information as to whether there is progression of the cancer or not—a space where oncologists need better, faster information. Still in its infancy, Lexent has a goal of having clinical validation done over the next cou- ple of years. This story originally appeared in the November 15, 2018, issue of Genetic Engineering & Biotechnology News (GEN) David Hong, M.D., VP of medical affairs and clinical development, Karius Phase Genomics is applying a novel approach to analyzing Hi-C data.

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