GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Disparities Within the Disparity-Determining HIV Risk Factors Among Latino Gay and Bisexual Men Attending a Community-Based Clinic in Los Angeles, CA.

BackgroundLatino gay, bisexual, and other men who have sex with men (MSM) in the United States have a 50% greater incidence of HIV when compared with White MSM. Previous studies have analyzed factors contributing to condomless anal intercourse among Latino MSM, but few studies have followed cohorts of HIV-negative Latino MSM to determine circumstances for HIV infection. Informed by Syndemics theory, we examine behavioral, biological, and contextual factors associated with HIV infection for Latino MSM.MethodsRisk assessment and HIV testing data were analyzed for all initially HIV negative, Latino MSM (n = 3111) visiting a community-based clinic in Los Angeles, CA from January 2009 to June 2014. Survival analyses were used to determine characteristics of Latino MSM who became HIV positive during the study time frame.ResultsSimilar to previous studies of MSM, self-reported history of chlamydia, gonorrhea, and/or syphilis (adjusted hazard ratio (aHR): 1.97; CI: 1.28 to 3.04), receptive condomless anal intercourse (aHR: 1.7; CI: 1.16 to 2.49), and methamphetamine use (aHR: 1.99; CI: 1.15 to 3.43) predicted HIV infection. In addition, originating from Central America (aHR: 2.31; CI: 1.41 to 3.79), Latino ethnicity of the last sex partner (aHR: 1.67; CI: 1.16 to 2.39) and experiencing intimate partner violence (IPV) (aHR: 1.73; CI: 1.13 to 2.64) were also associated with HIV infection among Latino MSM.ConclusionsThis is the first study to show independent associations between IPV and HIV infection among Latino MSM. This study shows that psychosocial conditions such as IPV fuel HIV incidence among Latino MSM, and psychosocial interventions should be considered to reduce HIV disparities among Latino MSM

Disparities Within the Disparity-Determining HIV Risk Factors Among Latino Gay and Bisexual Men Attending a Community-Based Clinic in Los Angeles, CA.

BackgroundLatino gay, bisexual, and other men who have sex with men (MSM) in the United States have a 50% greater incidence of HIV when compared with White MSM. Previous studies have analyzed factors contributing to condomless anal intercourse among Latino MSM, but few studies have followed cohorts of HIV-negative Latino MSM to determine circumstances for HIV infection. Informed by Syndemics theory, we examine behavioral, biological, and contextual factors associated with HIV infection for Latino MSM.MethodsRisk assessment and HIV testing data were analyzed for all initially HIV negative, Latino MSM (n = 3111) visiting a community-based clinic in Los Angeles, CA from January 2009 to June 2014. Survival analyses were used to determine characteristics of Latino MSM who became HIV positive during the study time frame.ResultsSimilar to previous studies of MSM, self-reported history of chlamydia, gonorrhea, and/or syphilis (adjusted hazard ratio (aHR): 1.97; CI: 1.28 to 3.04), receptive condomless anal intercourse (aHR: 1.7; CI: 1.16 to 2.49), and methamphetamine use (aHR: 1.99; CI: 1.15 to 3.43) predicted HIV infection. In addition, originating from Central America (aHR: 2.31; CI: 1.41 to 3.79), Latino ethnicity of the last sex partner (aHR: 1.67; CI: 1.16 to 2.39) and experiencing intimate partner violence (IPV) (aHR: 1.73; CI: 1.13 to 2.64) were also associated with HIV infection among Latino MSM.ConclusionsThis is the first study to show independent associations between IPV and HIV infection among Latino MSM. This study shows that psychosocial conditions such as IPV fuel HIV incidence among Latino MSM, and psychosocial interventions should be considered to reduce HIV disparities among Latino MSM

Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle

BACKGROUND: The vaginal microbial community plays a vital role in maintaining women\u2019s health. Understanding the precise bacterial composition is challenging because of the diverse and difficult-to-culture nature of many bacterial constituents, necessitating culture-independent methodology. During a natural menstrual cycle, physiological changes could have an impact on bacterial growth, colonization, and community structure. The objective of this study was to assess the stability of the vaginal microbiome of healthy Canadian women throughout a menstrual cycle by using cpn60-based microbiota analysis. Vaginal swabs from 27 naturally cycling reproductive-age women were collected weekly through a single menstrual cycle. Polymerase chain reaction (PCR) was performed to amplify the universal target region of the cpn60 gene and generate amplicons representative of the microbial community. Amplicons were pyrosequenced, assembled into operational taxonomic units, and analyzed. Samples were also assayed for total 16S rRNA gene content and Gardnerella vaginalis by quantitative PCR and screened for the presence of Mollicutes by using family and genus-specific PCR. RESULTS: Overall, the vaginal microbiome of most women remained relatively stable throughout the menstrual cycle, with little variation in diversity and only modest fluctuations in species richness. Microbiomes between women were more different than were those collected consecutively from individual women. Clustering of microbial profiles revealed the expected groupings dominated by Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus jensenii. Interestingly, two additional clusters were dominated by either Bifidobacterium breve or a heterogeneous mixture of nonlactobacilli. Direct G. vaginalis quantification correlated strongly with its pyrosequencing-read abundance, and Mollicutes, including Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum, were detected in most samples. CONCLUSIONS: Our cpn60-based investigation of the vaginal microbiome demonstrated that in healthy women most vaginal microbiomes remained stable through their menstrual cycle. Of interest in these findings was the presence of Bifidobacteriales beyond just Gardnerella species. Bifidobacteriales are frequently underrepresented in 16S rRNA gene-based studies, and their detection by cpn60-based investigation suggests that their significance in the vaginal community may be underappreciated.Peer reviewed: YesNRC publication: Ye

16S rRNA gene sequence and phylogenetic tree of lactobacillus species from the vagina of healthy Nigerian women

Background: The vaginal microbial community plays a vital role in maintaining women\u27s health. Understanding the precise bacterial composition is challenging because of the diverse and difficult-to-culture nature of many bacterial constituents, necessitating culture-independent methodology. During a natural menstrual cycle, physiological changes could have an impact on bacterial growth, colonization, and community structure. The objective of this study was to assess the stability of the vaginal microbiome of healthy Canadian women throughout a menstrual cycle by using cpn60-based microbiota analysis. Vaginal swabs from 27 naturally cycling reproductive-age women were collected weekly through a single menstrual cycle. Polymerase chain reaction (PCR) was performed to amplify the universal target region of the cpn60 gene and generate amplicons representative of the microbial community. Amplicons were pyrosequenced, assembled into operational taxonomic units, and analyzed. Samples were also assayed for total 16S rRNA gene content and Gardnerella vaginalis by quantitative PCR and screened for the presence of Mollicutes by using family and genus-specific PCR.Results: Overall, the vaginal microbiome of most women remained relatively stable throughout the menstrual cycle, with little variation in diversity and only modest fluctuations in species richness. Microbiomes between women were more different than were those collected consecutively from individual women. Clustering of microbial profiles revealed the expected groupings dominated by Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus jensenii. Interestingly, two additional clusters were dominated by either Bifidobacterium breve or a heterogeneous mixture of nonlactobacilli. Direct G. vaginalis quantification correlated strongly with its pyrosequencing-read abundance, and Mollicutes, including Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum, were detected in most samples.Conclusions: Our cpn60-based investigation of the vaginal microbiome demonstrated that in healthy women most vaginal microbiomes remained stable through their menstrual cycle. Of interest in these findings was the presence of Bifidobacteriales beyond just Gardnerella species. Bifidobacteriales are frequently underrepresented in 16S rRNA gene-based studies, and their detection by cpn60-based investigation suggests that their significance in the vaginal community may be underappreciated

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe