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Genomics in the Journals Nov 6, 2014

NEW YORK (GenomeWeb) – A team from Japan and the US used a combination of whole-genome sequencing, exome sequencing, and "oncovirome" sequencing to scrutinize matched tumor and normal samples from more than 500 individuals from different populations who had a form of liver cancer called hepatocellular carcinoma.

As they reported in Nature Genetics, the researchers considered tumor-normal pairs from 413 Japanese individuals with liver cancer and 90 tumor-normal pairs from American liver cancer patients for work done through the International Cancer Genome Consortium. Fifteen of the cases were classified as intrahepatic cholangiocarcinoma (a type of liver cancer linked to liver fluke infection), while the remaining cases were HCC.

In an attempt to tease apart epidemiological and population-related contributors to these liver cancers, the team did exome sequencing on 452 tumor-normal pairs, genome sequencing on 22 of the HCC pairs, and oncovirus sequencing on 198 of the liver cancer cases.

The latter search uncovered instances of infection with hepatitis B virus, the human papillomaviruses HPV-16 and HPV-18, and human T-lymphotrophic virus, while tumor sequence and copy number analyses highlighted viral insertion sites, dozens of potential driver genes, and 11 pathways with apparent ties to liver cancer.

By incorporating data for 105 more HCC cases assessed by members of the Cancer Genome Atlas, meanwhile, the investigators got a glimpse at some of the mutation signatures and viral features found in liver tumors from individuals of Japanese, European, or Asian-American ancestry.

Researchers from the US and Nepal did whole-genome sequence typing and phylogenetic analysis on more than 100 Vibrio cholerae isolates from the O1 serotype in an effort to understand the history and aftermath of the 2010 Haitian cholera epidemic — work they described in mBio.

The team tracked down and verified SNPs in genome sequence data for 116 V. cholerae O1 isolates, including dozens of isolates involved in or related to strains from the outbreak in Haiti.

Using these variants, together with other alterations and genomic rearrangements, investigators unraveled relationships between the cholera-causing isolates. Their findings were consistent with the notion that V. cholerae was introduced to Haiti from Nepal during a single event, which was followed by fast and widespread expansions of V. cholerae clones within Haiti.

"As eradication efforts move forward, phylogeographic knowledge will be important for identifying persistent sources and monitoring success at regional levels," senior author Paul Keim, a researcher affiliated with Northern Arizona University and the Translational Genomics Research Institute, and his colleagues wrote.

"The results of molecular and epidemiological analyses of this outbreak suggest that an indigenous Haitian source of V. cholerae is unlikely," they added, "and that an indigenous source has not contributed to the genome evolution of this clade."

A GigaScience study by researchers in Russia, Australia, Canada, and the US introduced a web-based platform for analyzing and sharing genomic data between groups while maintaining study participants' privacy.

The tool — dubbed Genome-wide Association Tracks Chromosome Highway, or GWATCH — is reportedly an automated approach designed for finding and verifying genes and genetic variants that contribute to the risk of inherited and infectious diseases — from heart disease and cancer to human papillomavirus and HIV infection — with the help of visualization tools that include a three-dimensional "chromosome highway."

Along with the visualization aspects of the tool, GWATCH is designed to provide researchers with access to human genomic information in a privacy-protected manner that obscures personal identifiers and raw data.

In their proof-of-principle paper, researchers demonstrated GWATCH's utility for finding genes involved in features of HIV infection or AIDS using data from three different genome-wide association studies. They noted that "association datasets from any [GWAS or whole-genome sequence] study can be uploaded and analyzed by GWATCH."

In the American Journal of Human Genetics, an international team led by investigators at the Harvard School of Public Health and the Broad Institute began parsing out the contributions that regulatory variants and variants with cell type-specific functions make to common disease heritability.

Using "variance-component" computational strategies — applied to simulated SNP data and variants identified or imputed for more than 100,000 individuals participating in case-control trials of 11 common conditions or traits considered by the Wellcome Trust Case Control Consortium — the researchers teased apart the heritability that could be attributed to SNPs falling in various functional groups.

Heritability associated with imputed regulatory variants was more pronounced than that linked to variants that had been directly genotyped, the study's authors noted, while SNPs falling in protein-coding sequences appeared to account for less than 10 percent of the heritability detected for the common diseases.

"We have demonstrated through extensive simulations that our variance-component strategy yields robust estimates that account for [linkage disequilibrium] between categories and complex disease architecture," they wrote, adding that "our approach provides a means of assessing biological hypotheses of contributions to disease heritability."