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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30 Clinical OMICs January/February 2019 www.clinicalomics.com A dvances in precision medicine are determined, in large part, by the ability to more carefully and completely analyze and understand the genome. This requires new developments in how we look at DNA that go way beyond sequencing data. The new developments in this space promise limitless creativity and versatility, from methods that detect DNA in such small amounts that rare variants can be found, to tools that uncover the 3D architecture of the genome to facil- itate further insights into structural variation. Such advances could dramatically improve patient outcomes by allowing clinicians to fol- low a tumor 's progression through a simple blood draw, or discover a bacterial infection before the patient even feels sick. The work at the forefront of precision medicine is orig- inal, exciting, transformative, and moving at breakneck speed. Knowing the Locations of Loci Could Transform Genomics The structural variation of the genome is a hot topic, with many companies developing novel ways of making strides in this area. One such company, Phase Genomics, located in Seattle, WA, has developed a library preparation kit that has the potential to transform genome science. The approach used by Phase Genomics to study the 3D architecture of genomes comes from work done in the lab- oratory of Jay Shendure, M.D., Ph.D., professor of genome sciences at the University of Washington. The method is based on Hi-C, which was first developed about a decade ago in the laboratories of Job Dekker, Ph.D., professor of biochemistry and molecular pharmacology at the Univer- sity of Massachusetts Medical School, and Eric Lander, Ph.D., professor of biology at the Massachusetts Institute of Technology. "Although Hi-C has been around for a while, the way that Phase Genomics is applying it is novel," said Ivan Liachko, Ph.D., and CEO of Phase Genomics. "Hi-C data is somewhat esoteric, but extremely powerful. It provides an orthogonal datatype that can supplement all sorts of genomic efforts." Hi-C starts by crosslinking the DNA within intact cells, causing interacting loci to bind to one another before sequencing. In sequencing the junctions that are formed, Hi-C allows the capture of the sequences that are physically close to each other in the cell. There are multiple applications for this type of sequence analysis, one of which is assembling a genome with ultralong genomic contiguity without the requirement of high molecular weight DNA. Indeed, Phase Genomics, in collaboration with PacBio, published the goat genome last year—the highest contiguity de novo genome ever assem- bled. And during the second week of October this year, PacBio announced that it has produced the most contiguous diploid human genome assembly of a single individual to date, representing the nearly complete DNA sequence from all 46 chromosomes inherited from both parents. This was done, again, using technology from Phase Genomics. An additional application is in microbiome research, enabling the identification of which specific sequences start in the same cell from a large, heterogeneous sample of bac- teria and other microbes. This is especially important when dealing with mobile elements such as plasmids or trans- posons—pieces of DNA that can move antibiotic resistance genes from species to species. "Because the crosslinks occur inside intact cells, any two loci that interact by Hi-C must have originated in the same cell, and this data can be used to deconvolute high-quality genomes directly from mixed populations," explained Liachko. Beyond Sequencing New Approaches to Examining DNA Are Helping to Advance Precision Medicine By Julianna LeMieux, Ph.D. "Hi-C data is somewhat esoteric, but extremely powerful. It provides an orthogonal datatype that can supplement all sorts of genomic efforts." —Ivan Liachko, Ph.D. CEO, Phase Genomics

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