Network deconvolution as a general method to distinguish direct dependencies in networks

Recognizing direct relationships between variables connected in a network is a pervasive problem in biological, social and information sciences as correlation-based networks contain numerous indirect relationships. Here we present a general method for inferring direct effects from an observed correlation matrix containing both direct and indirect effects. We formulate the problem as the inverse of network convolution, and introduce an algorithm that removes the combined effect of all indirect paths of arbitrary length in a closed-form solution by exploiting eigen-decomposition and infinite-series sums. We demonstrate the effectiveness of our approach in several network applications: distinguishing direct targets in gene expression regulatory networks; recognizing directly interacting amino-acid residues for protein structure prediction from sequence alignments; and distinguishing strong collaborations in co-authorship social networks using connectivity information alone. In addition to its theoretical impact as a foundational graph theoretic tool, our results suggest network deconvolution is widely applicable for computing direct dependencies in network science across diverse disciplines.National Institutes of Health (U.S.) (grant R01 HG004037)National Institutes of Health (U.S.) (grant HG005639)Swiss National Science Foundation (Fellowship)National Science Foundation (U.S.) (NSF CAREER Award 0644282

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Determinantes nutricionais e sóciodemográficos da variação de peso no pós-parto: uma revisão da literatura Nutritional and socio-demographic determinants of post-partum weight change: a literature review

Trata-se de um estudo de revisão sobre os fatores nutricionais e sócio-demográficos da variação de peso no pós-parto. Foi realizada uma busca bibliográfica nas bases de dados eletrônicas Scientific Eletronic Library On-line (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Medical Literature Analysis and Retrieval System Online (MEDLINE) referente a literatura publicada na última década (1997-2008). Treze artigos, um informe técnico e dois livros considerados relevantes sobre o assunto e publicados anteriormente ao ano 1997 foram citados na revisão. A revisão priorizou estudos de ensaios clínicos randomizados e de seguimento realizados com gestantes e mulheres no pós-parto. Os resultados obtidos mostram como principais fatores associados com a variação de peso no pós-parto o ganho de peso gestacional acima das recomendações do Institute of Medicine, Índice de Massa Corporal Pré-Gestacional > 25 kg/m2, dieta, tempo e intensidade do aleitamento materno e os fatores sócio-demográficos: raça negra, primiparidade, idade materna, baixa renda e baixa escolaridade. A prática regular de atividade física é recomendada como uma estratégia para evitar o ganho de peso excessivo e melhorar a perda de peso durante o pós-parto. No Brasil não existe uma estratégia nacional para prevenir o ganho de peso excessivo e garantir a adequada perda de peso nesse período. Durante o pós-parto, a maioria das ações de saúde visa basicamente garantir o aleitamento materno.<br>This study is a review of nutritional and sociodemographic factors determining post-partum weight variation. A bibliographical search was carried out on the electronic databases Scientific Eletronic Library On-line (SciELO), Latin-American and Caribbean Literature on Health Sciences (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE) for titles published in the past decade (1997-2008). Thirteen articles, one technical note and two books considered relevant to the subject and published prior to 1997 are also cited in the review. The review prioritized studies involving randomized clinical trials and follow-up carried out among pregnant and post-partum women. The results show that the following are the main factors associated with post-partum weight variation: gestational weight gain above the recommendations of the Institute of Medicine, Pregestational Body Mass > 25 kg/m2, diet, duration and intensity of breast-feeding and socio-demographic factors, such as being black, having given birth only once, the age of the mother, low income and low schooling. Regular physical activity is recommended as a strategy for avoiding excessive weight gain and improving weight loss during post partum. In Brazil, there is no national strategy for preventing excessive weight gain and ensuring adequate weight loss during this period. During post-partum, most health service actions are restricted to ensuring that mothers breastfeed