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Genomics in the Journals Sep 18, 2014

NEW YORK (GenomeWeb) – In BMC Biology, investigators involved with the Human Microbiome Project discussed the collection of DNA viruses that they found when sampling diverse body sites from more than 100 healthy adult volunteers.

The team tested this component of the healthy human virome through a series of deep metagenomic sequencing experiments on 702 nose, mouth, skin, stool, and/or vaginal samples from 102 individuals between the ages of 18 and 40 years old with no apparent symptoms of infection. For nearly half of those participants, samples were taken at two or more time points spaced out over around a month to more than a year.

When they scrutinized the double-stranded and single-stranded virus DNA data, the researchers found that 92 percent of participants carried sequences from at least one virus. In some cases, as many as 10 or 15 different viruses turned up in the same individual.

Those viruses ranged from innocuous to possibly pathogenic, they reported. Some turned up transiently, while others seemed to signify low-level, asymptomatic infections that were fairly stable over time, contributing to the viral "fingerprint" that each individual carried.

The analysis also uncovered new forms of known viruses. For instance, the team saw strains of herpesvirus in many mouth microbiomes that appeared distinct from sexually transmitted forms of herpesvirus. A subset of the skin and nose samples contained papillomaviruses resembling those described in non-human hosts, meanwhile, though some vaginal samples yielded sequences stemming from well known strains of human papillomavirus such as HPV16, 18, and 45 that have been implicated in cervical cancer.

"It's very important to know what viruses are present in a person without causing a problem and what viruses could be responsible for serious illnesses that need medical attention," co-author Gregory Storch, a pediatrics researcher at Washington University School of Medicine, said in a statement. "While more research remains, we now have a much clearer picture of the communities of viruses that naturally exist in healthy people."


A team from the University of Maryland and the National Institute of Allergy and Infectious Diseases turned to single-molecule, real-time (SMRT) Pacific Biosciences sequencing, Illumina sequencing, and a range of genome assembly methods when considering strategies for putting together a de novo genome assembly using limited DNA inputs found in a clinical sample of the filarial nematode worm Loa loa — known for causing a serious eye infection called an African eye worm, or loiasis.

As they reported in BMC Genomics, the researchers generated L. loa reads with both the PacBio RSII and Illumina MiSeq instruments in an effort to come up with a low DNA input assembly for the genome that met or exceeded the quality of a 91.4 million base L. loa genome produced from Roche 454 reads and described in Nature Genetics last year.

After testing half a dozen different assembly methods that incorporated PacBio and Illumina reads used alone or in combination, the team settled on a final L. loa genome assembly comprised exclusively of PacBio reads that spanned some 96.4 million bases.

The new assembly is comprised of longer continuous stretches of DNA, or contigs, than the original assembly for that filarial worm, prompting enthusiasm about the prospect of applying the same sequencing strategy to other clinical samples in the future.

"Recent improvements in long-read, single-molecule sequencing have enabled more economical sequencing and improved genome assembly for previously difficult to sequence clinical samples," first author Luke Tallon, a researcher with the University of Maryland School of Medicine's Institute for Genome Sciences, said in a statement.


A Nature Genetics study by investigators in the US, UK, and elsewhere described almost two-dozen previously undetected prostate cancer risk loci.

Through a meta-analysis of genotyping patterns at more than 10 million SNPs in the genomes of 43,303 individuals with prostate cancer and 43,737 without, the researchers focused in on 23 loci that appeared to bump up prostate cancer risk. Samples for the study were drawn from European, African, Japanese, and Latino populations.

A closer look at the new risk loci suggested that at least seven of the sites conferred prostate cancer risk in individuals from multiple ethnic backgrounds. Sixteen more sites were associated with prostate cancer in European men, the team found, including one locus that was linked to early-onset prostate cancer.

Along with risk variants described for prostate cancer in the past, the newly detected loci seem to explain roughly one-third of prostate cancer's heritability in individuals of European descent, the study's authors noted.

Moreover, they argued, the results "provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease."


Non-caloric artificial sweetener appears capable of altering the mammalian gut microbiome in ways that can contribute to glucose intolerance, a risk factor for diabetes, according to a new Nature study.

After identifying apparent metabolic problems in mice whose food had been spiked with sweeteners such as saccharin, sucralose, or aspartame, a team based at the Weizmann Institute of Science and other centers in Israel decided to take a closer look at the saccharin-related effects, which were particularly pronounced in those initial mouse experiments.

From antibiotic treatment tests, fecal transplant experiments, and 16S ribosomal RNA sequencing analyses on stool samples from untreated control mice and mice fed glucose or saccharin, the researchers saw signs that the mouse gut microbiome was mediating the metabolic effects of the artificial sweetener.

When they folded in information on hundreds of non-diabetic individuals from Israel who are participating in an ongoing Personalized Nutrition Project, the investigators saw similar ties between self-reported artificial sweetener consumption, diminished glucose tolerance, and gut microbial community membership.

Among the gut microbiome changes the team described were a boost in Bacteroides bacteria and a decline in bugs from a bacterial order called Clostridiales — microbial patterns that resemble those associated with type 2 diabetes in prior human studies.

"Our relationship with our own individual mix of gut bacteria is a huge factor in determining how the food we eat affects us," senior author Eran Elinav, an immunology researcher at the Weizmann Institute of Science, said in a statement.

"Especially intriguing is the link between use of artificial sweeteners — through the bacteria in our guts — to a tendency to develop the very disorders they were designed to prevent," Elinav added. "[T]his calls for reassessment of today's massive, unsupervised consumption of these substances."

The Scan

Missed Early Cases

A retrospective analysis of blood samples suggests early SARS-CoV-2 infections may have been missed in the US, the New York Times reports.

Limited Journal Editor Diversity

A survey finds low diversity among scientific and medical journal editors, according to The Scientist.

How Much of a Threat?

Science writes that need for a provision aimed at shoring up genomic data security within a new US bill is being questioned.

PNAS Papers on Historic Helicobacter Spread, Brain Development, C. difficile RNAs

In PNAS this week: Helicobacter genetic diversity gives insight into human migrations, gene expression patterns of brain development, and more.