Network-based stratification of tumor mutations.

Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence

Psi-floor diagrams and a Caporaso-Harris type recursion

Floor diagrams are combinatorial objects which organize the count of tropical plane curves satisfying point conditions. In this paper we introduce Psi-floor diagrams which count tropical curves satisfying not only point conditions but also conditions given by Psi-classes (together with points). We then generalize our definition to relative Psi-floor diagrams and prove a Caporaso-Harris type formula for the corresponding numbers. This formula is shown to coincide with the classical Caporaso-Harris formula for relative plane descendant Gromov-Witten invariants. As a consequence, we can conclude that in our case relative descendant Gromov-Witten invariants equal their tropical counterparts.Comment: minor changes to match the published versio

Developmental course of autistic social impairment in males

BACKGROUND: Recent research has suggested that autistic social impairment (ASI) is continuously distributed in nature, and that subtle autistic-like social impairments aggregate in the family members of children with pervasive developmental disorders (PDDs). This study examined the longitudinal course of quantitatively-characterized ASI in 3 to 18 year old boys with and without PDD. METHODS: We obtained assessments of 95 epidemiologically ascertained male-male twin pairs and a clinical sample of 95 affected children using the Social Responsiveness Scale (SRS), at two time points, spaced 1–5 years apart. Longitudinal course was examined as a function of age, familial loading for PDD, and autistic severity at baseline. RESULTS: Inter-individual variation in SRS scores was highly preserved over time, with test-retest correlation of 0.90 for the entire sample. SRS scores exhibited modest general improvement over the study period; individual trajectories varied as a function of severity at baseline and were highly familial. CONCLUSION: Quantitative measurements of ASI reflect heritable trait-like characteristics. Such measurements can serve as reliable indices of phenotypic severity for genetic and neurobiologic studies, and have potential utility for ascertaining incremental response to intervention

Women’s expectations and experiences of rupture of membranes and views of the potential use of reagent pads for detecting amniotic fluid

AIMS: To explore first time mothers’ expectations and experiences regarding rupture of membranes (RoM) at term, and their views on the potential use of reagent pads that detect amniotic fluid. BACKGROUND: There is little information available on women’s experiences of spontaneous rupture of membranes, or interest in utilising methods to confirm rupture of membranes (e.g. reagent pads). DESIGN: Descriptive qualitative study, utilising focus groups and telephone interviews with women during pregnancy and after the birth of their first baby. Thematic analysis was undertaken to analyse women’s responses. METHODS: Ethics committee approval was obtained. Twenty-five women participated in the study of whom 13 contributed both during pregnancy and postpartum between October 2015 and March 2016. FINDINGS: Three overarching themes emerged from the data from women’s expectations and experiences: uncertainty in how, when and where membranes may rupture; information which was felt to be limited and confirmation of rupture of membranes. The potential use of reagent pads met with varied responses. CONCLUSION: Women were interested in having facts and figures regarding RoM, such as characteristics of liquor; volume and probability of membranes rupturing spontaneously at term. Use of a pad as a means of confirmation was viewed as helpful, although the potential for increasing anxiety was raised

Tropical ψ\psi classes

We introduce a tropical geometric framework that allows us to define $\psi$ classes for moduli spaces of tropical curves of arbitrary genus. We prove correspondence theorems between algebraic and tropical $\psi$ classes for some one-dimensional families of genus-one tropical curves

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN