Clinical OMICS

NOV-DEC 2017

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 32 of 47 November/December 2017 Clinical OMICs 31 CombiMatrix Presents Data from Genomic Abnormalities Study CombiMatrix has presented new data from a first-of-its kind study showing that genomic alterations decrease in frequency and severity from conception through development into childhood. The study—which analyzed nearly 32,000 samples—was intended to provide a comprehensive assessment of chromo- somal imbalances and their adverse impact upon human growth and devel- opment from conception to childhood. " These results support the impor- tance of genomic testing for different abnormalities that may occur at distinct development stages," CombiMatrix Pres- ident and CEO Mark McDonough said in a statement. "We now have even more compelling evidence of the importance of the genetic information produced from this testing from preconception through early childhood." Among key findings of the study: • Embryo or early pregnancy loss sam- ples showed the highest abnormality rates and a predictable correlation between the severity of chromosomal abnormalities, primarily aneuploid- ies, with unsuccessful implantation or progression to viable pregnancy. • Prenatal and neonatal samples showed that the frequency of signif- icant genomic alterations correlated with the incidence of significant physical and developmental abnor- malities, but were not necessarily incompatible with life. • Pediatric samples were predomi- nantly deletions and duplications rather than aneuploidy and had less drastic adverse effects. ciated variants previously identified by genome-wide association studies (GWAS) overlapped with eQTLs. According to Stephen Montgomery, a Stanford University professor and GTEx investigator, this suggests there are expression mechanisms under- lying those trait associations. "That actually gives us quite a lot of infor- mation to move forward with about what molecular mechanisms underlie complex diseases," he added. In another analysis, researchers examined how rare variants, which may play an important role in deter- mining individual disease risk, impacted gene expression. By pin- pointing outliers—genes that were expressed at extremely high or low levels—in the GTEx dataset, the team discovered that these outliers were more likely to have a rare variant nearby than their counterparts. A Global Resource The consortium has made their data publically available for research- ers to access. This catalogue of raw and unprocessed data is a "fantastic resource for the research community," Ward said. The group is also maintain- ing a biobank of the analysed tissue samples. However, the atlas does have its limitations. For example, Brown pointed out, the group analyzed het- erogeneous tissues, rather than single cells. "I think the next big leap will be true cellular-level resolution," he said. Another limitation, according to Ward, is that "while this dataset pro- vides insight into the associations between genetic variants and gene expression, I think more work is needed to determine the causality." One way scientists could do this, she noted, is by using techniques like CRISPR/Cas9 gene editing. The release of the next version of the GTEx atlas, which researchers expect to publish sometime next year, will more than double the sample size, Brown said. This will allow research- ers to address some questions that are difficult to probe with the currently available sample. Brown, for one, is interested in examining more of the trans-QTLs. In addition to analyzing tissues from more patients, some of the mem- bers of the consortium are working on characterizing additional factors, such as DNA methylation, protein abundance, alternative splicing, and telomere length, by applying diverse molecular assays to the available sam- ples. This effort, dubbed "Enhancing GTEx," will publish analyses associ- ated with their data over the next two years, according to Montgomery. Ultimately, pooling all this infor- mation could help benefit person- alized medicine, "It could be in the future that you go and you have your genome taken, but you might get your blood transcriptome, your metabo- lome, your proteome—all these other types of data," he added. "So if we build the [analytical] infrastructure now, we should get better predictions for indi- viduals about genetic risk factors." "All biomedical researchers should welcome the wealth of data that con- tinues to be released by the GTEx proj- ect, and the insights it provides into the regulatory code of our genomes," Nature's editors wrote in a recent edi- torial. "It is an important step towards the ultimate and ambitious goal of being able to characterize genetic vari- ation and gene regulation in all cells of the human body." BlackJack3D / Getty Images

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