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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32 Clinical OMICs January/February 2019 www.clinicalomics.com "Taking an NGS approach yields more exact informa- tion," Hong said. "It not only tells us if an infection is pres- ent, it also tells us exactly what is causing the infection. This information is incredibly useful for a clinician who needs to know how to effectively treat infections." In early October, Karius released results of a clinical trial, PREDSEQ, that started roughly one year ago. Working in conjunction with St. Jude Children's Research Hospital in Memphis, TN, the pilot study enrolled high-risk pediatric leukemia patients. Hong indicates that the study was trying to "answer the question of whether a pathogen was pres- ent before it was able to be cultured." Indeed, the results showed that Karius could detect a pathogen two to four days prior to clinical symptoms, providing proof of concept of a tool that can identify patients who are about to get sick. The test developed by Karius can accurately detect patho- gens in diagnostically challenging or culture-negative infec- tions or in deep-seated infections where cultures are hard to obtain. Additionally, it could allow for immunocompro- mised patients to be more actively monitored and for anti- microbial therapies to be more precisely determined. The Karius system detects traces of pathogen cfDNA in plasma samples after sifting through the enormous bulk of human cfDNA. The system also has to discount cfDNA from commensal bacteria present in the human microbiome. Essentially the system finds the proverbial needle in the haystack, and it does so by using agnostic whole-genome processing while eschewing primers and probes. According to Hong, "Karius curated its database of pathogens to include common pathogens of immunocom- promised patients and others that are notoriously difficult to diagnose such as the non-Aspergillus fungal species." Looking ahead, Hong imagines a world where high-risk patients are treated preemptively for their infections, based on their NGS results—similar to how stem cell patients are treated now with the constant monitoring of their cytomeg- alovirus antibody titers. Adding Precision to Sequencing While the goal of some companies may be to sequence as many people as possible, Mission Bio's goal is much smaller, but not any less significant. Charlie Silver, cofounder and CEO, said that Mission Bio is "the only company that sequences DNA mutations in every cell in the sample" and that is driven by the idea that it can "sensitively assay and determine all of the clones that are pres- ent in a tumor." By doing that, the company can, he asserts, "better line up pre- cision medicines and the right combinations to be able to more effectively treat patients." Mission Bio's technology is derived from research that was conducted in 2014 in the laboratory of Adam Abate, Ph.D., associate professor of bioengineering at the Univer- sity of California, San Francisco. The company's platform, called Tapestri, uses microfluidics to partition thousands of cells into individual droplets. Each cell, then, occupies its own miniature reaction vessel. The cell is lysed, and its DNA is combined with barcoded beads, primers, and other reagents. The barcode indicates the cell's identity and muta- tional profile. After thermal cycling, the product that comes out of Tap- estri can be processed in NGS workflows, generating clonal information that may be analyzed by Mission Bio software. The Mission Bio system results in high-throughput sin- gle-cell DNA mutation sequencing and characterizes cell- to-cell genomic heterogeneity. In cancer patients, this information could be used to mea- sure treatment outcomes or guide tweaks to treatment proto- cols. "In almost all tumor populations, there is fundamental genetic heterogeneity that exists," said Dennis Eastburn, Ph.D., cofounder and CSO at Mission Bio. "Bulk sequencing provides an average of the genetic varients found in a sam- ple, but you might miss the genetic diversity between cells." "Our method," he asserted, "enables rapid and cost-effec- tive targeted genome sequencing of thousands of tumor cells (continued from previous page) Lexent Bio will use a blood-only approach to monitor cancer treatment efficacy by providing the methylation status of patients' cell-free DNA (cfDNA).

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