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Computable phenotype

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https://www.readbyqxmd.com/read/28327993/stepwise-distributed-open-innovation-contests-for-software-development-acceleration-of-genome-wide-association-analysis
#1
Andrew Hill, Po-Ru Loh, Ragu B Bharadwaj, Pascal Pons, Jingbo Shang, Eva Guinan, Karim Lakhani, Iain Kilty, Scott A Jelinsky
BACKGROUND: The association of differing genotypes with disease related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low cost genotyping and sequencing has made collecting large scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies are being used to capture numerous new and complex phenotypic descriptors...
February 28, 2017: GigaScience
https://www.readbyqxmd.com/read/28327978/a-dataset-of-images-and-morphological-profiles-of-30-000-small-molecule-treatments-using-the-cell-painting-assay
#2
Mark-Anthony Bray, Sigrun M Gustafsdottir, Vebjorn Ljosa, Shantanu Singh, Katherine L Sokolnicki, Joshua A Bittker, Nicole E Bodycombe, Vlado Dancík, Thomas P Hasaka, C Suk-Yee Hon, Melissa M Kemp, Kejie Li, Deepika Walpita, Mathias J Wawer, Todd R Golub, Stuart L Schreiber, Paul A Clemons, Alykhan F Shamji, Anne E Carpenter
Background: Large-scale image sets acquired by automated microscopy of perturbed samples enable a detailed comparison of cell states induced by each perturbation, such as a small molecule from a diverse library. Highly multiplexed measurements of cellular morphology can be extracted from each image and subsequently mined for a number of applications. Findings: This microscopy data set includes 919,874 five-channel fields of view representing 30,616 tested compounds, available at 'The Cell Image Library' repository...
January 7, 2017: GigaScience
https://www.readbyqxmd.com/read/28322827/structural-divergence-of-essential-triad-ribbon-synapse-proteins-among-placental-mammals-implications-for-preclinical-trials-in-photoreceptor-transplantation-therapy
#3
Christopher R J Laver, Joanne A Matsubara
As photoreceptor transplantation rapidly moves closer to the clinic, verifying graft efficacy in animal models may have unforeseen xenogeneic barriers. Although photoreceptor transplants have most convincingly exhibited functional synaptogenesis in conspecific studies, such evidence (while ruling out false-positives due to: viral graft labeling, fusion/cytosolic transfer, or neuroprotection) has not yet been shown for discordant xenografts. From this, a fundamental question should be raised: is useful xenosynaptogenesis likely between human photoreceptors and mouse retina? The triad ribbon synapse (TRS) that would normally form is unique and contains trans-synaptic proteins essential to its formation and function...
March 18, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28319199/a-computational-analysis-of-in-vivo-vegfr-activation-by-multiple-co-expressed-ligands
#4
Lindsay E Clegg, Feilim Mac Gabhann
The splice isoforms of vascular endothelial growth A (VEGF) each have different affinities for the extracellular matrix (ECM) and the coreceptor NRP1, which leads to distinct vascular phenotypes in model systems expressing only a single VEGF isoform. ECM-immobilized VEGF can bind to and activate VEGF receptor 2 (VEGFR2) directly, with a different pattern of site-specific phosphorylation than diffusible VEGF. To date, the way in which ECM binding alters the distribution of isoforms of VEGF and of the related placental growth factor (PlGF) in the body and resulting angiogenic signaling is not well-understood...
March 20, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28318622/computer-assisted-topological-analysis-of-renal-allograft-inflammation-adds-to-risk-evaluation-at-diagnosis-of-humoral-rejection
#5
Antoine Sicard, Vannary Meas-Yedid, Maud Rabeyrin, Alice Koenig, Stephanie Ducreux, Frederique Dijoud, Valerie Hervieu, Lionel Badet, Emmanuel Morelon, Jean Christophe Olivo-Marin, Valerie Dubois, Olivier Thaunat
Antibody-mediated rejection is associated with heterogeneous kidney allograft outcomes. Accurate evaluation of risk for graft loss at time of diagnosis is necessary to offer personalized treatment. In contrast with serological and molecular assessment, morpho-histological evaluation of antibody-mediated rejection lesions has not significantly evolved. This relies on Banff classifications designed to be of diagnostic discriminatory power rather than prognostic and face quantitative and qualitative limitations...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28316067/fisse-a-simple-non-parametric-test-for-the-effects-of-a-binary-character-on-lineage-diversification-rates
#6
Daniel L Rabosky, Emma E Goldberg
It is widely assumed that phenotypic traits can influence rates of speciation and extinction, and several statistical approaches have been used to test for correlations between character states and lineage diversification. Recent work suggests that model-based tests of state-dependent speciation and extinction are sensitive to model inadequacy and phylogenetic pseudoreplication. We describe a simple non-parametric statistical test ("FiSSE") to assess the effects of a binary character on lineage diversification rates...
March 18, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28315880/an-analytic-solution-to-the-computation-of-power-and-sample-size-for-genetic-association-studies-under-a-pleiotropic-mode-of-inheritance
#7
Derek Gordon, Douglas Londono, Payal Patel, Wonkuk Kim, Stephen J Finch, Gary A Heiman
Our motivation here is to calculate the power of 3 statistical tests used when there are genetic traits that operate under a pleiotropic mode of inheritance and when qualitative phenotypes are defined by use of thresholds for the multiple quantitative phenotypes. Specifically, we formulate a multivariate function that provides the probability that an individual has a vector of specific quantitative trait values conditional on having a risk locus genotype, and we apply thresholds to define qualitative phenotypes (affected, unaffected) and compute penetrances and conditional genotype frequencies based on the multivariate function...
March 18, 2017: Human Heredity
https://www.readbyqxmd.com/read/28314113/genome-wide-estimation-of-heritability-and-its-functional-components-for-flowering-defense-ionomics-and-developmental-traits-in-a-geographically-diverse-population-of-i-arabidopsis-thaliana-i
#8
Rong-Cai Yang
Narrow-sense heritability (portion of the total phenotypic variation due to additive genetic effect, <i>h</i><sup>2</sup>) is a critical parameter in plant breeding and genetics, but its estimation is difficult for populations with unknown pedigree information. This study applied a marker-based linear mixed model (LMM) analysis to estimate narrow-sense heritability and its seven functional components corresponding to SNPs in coding and noncoding regions for each of 107 flowering, defense, ionomics and developmental traits in an Arabidopsis (<i>Arabidopsis thaliana</i>) population of 199 inbred lines with unknown genetic relatedness...
March 17, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28306160/new-approach-shows-no-association-between-maternal-milk-fatty-acid-composition-and-childhood-wheeze-or-asthma
#9
Chad A Logan, Stephanie Brandt, Martin Wabitsch, Hermann Brenner, Frank Wiens, Bernd Stahl, Tamás Marosvölgyi, Tamás Decsi, Dietrich Rothenbacher, Jon Genuneit
BACKGROUND: Previous observational studies have implied breast milk fatty acid composition may play a role in development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach...
March 17, 2017: Allergy
https://www.readbyqxmd.com/read/28302587/transcriptomic-changes-in-cho-cells-after-adaptation-to-suspension-growth-in-protein-free-medium-analysed-by-a-species-specific-microarray
#10
Smriti Shridhar, Gerald Klanert, Norbert Auer, Inmaculada Hernandez-Lopez, Maciej M Kańduła, Matthias Hackl, Johannes Grillari, Nancy Stralis-Pavese, David P Kreil, Nicole Borth
Chinese Hamster Ovary (CHO) cells are the preferred cell line for production of biopharmaceuticals. These cells are capable to grow without serum supplementation, but drastic changes in their phenotype occur during adaptation to protein-free growth, which typically include the change to a suspension phenotype with reduced growth rate. A possible approach to understand this transformation, with the intention to counteract the reduction in growth by targeted supplementation of protein-free media, is gene expression profiling...
March 13, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28302069/bioinformatics-identification-of-new-targets-for-improving-low-temperature-stress-tolerance-in-spring-and-winter-wheat
#11
Alain B Tchagang, François Fauteux, Dan Tulpan, Youlian Pan
BACKGROUND: Phenotypic studies in Triticeae have shown that low temperature-induced protective mechanisms are developmentally regulated and involve dynamic acclimation processes. Understanding these mechanisms is important for breeding cold-resistant wheat cultivars. In this study, we combined three computational techniques for the analysis of gene expression data from spring and winter wheat cultivars subjected to low temperature treatments. Our main objective was to construct a comprehensive network of cold response transcriptional events in wheat, and to identify novel cold tolerance candidate genes in wheat...
March 16, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28301675/review-article-bioinformatics-an-overview-and-its-applications
#12
W J S Diniz, F Canduri
Technological advancements in recent years have promoted a marked progress in understanding the genetic basis of phenotypes. In line with these advances, genomics has changed the paradigm of biological questions in full genome-wide scale (genome-wide), revealing an explosion of data and opening up many possibilities. On the other hand, the vast amount of information that has been generated points the challenges that must be overcome for storage (Moore's law) and processing of biological information. In this context, bioinformatics and computational biology have sought to overcome such challenges...
March 15, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28301550/mammary-epithelial-cell-phenotype-disruption-in-vitro-and-in-vivo-through-eralpha36-overexpression
#13
Charlène Thiebaut, Clémence Chamard-Jovenin, Amand Chesnel, Chloé Morel, El-Hadi Djermoune, Taha Boukhobza, Hélène Dumond
Estrogen receptor alpha 36 (ERα36) is a variant of the canonical estrogen receptor alpha (ERα66), widely expressed in hormone sensitive cancer cells and whose high expression level correlates with a poor survival prognosis for breast cancer patients. While ERα36 activity have been related to breast cancer progression or acquired resistance to treatment, expression level and location of ERα36 are poorly documented in the normal mammary gland. Therefore, we explored the consequences of a ERα36 overexpression in vitro in MCF-10A normal mammary epithelial cells and in vivo in a unique model of MMTV-ERα36 transgenic mouse strain wherein ERα36 mRNA was specifically expressed in the mammary gland...
2017: PloS One
https://www.readbyqxmd.com/read/28301067/progressive-iron-accumulation-across-multiple-sclerosis-phenotypes-revealed-by-sparse-classification-of-deep-gray-matter
#14
Ahmed M Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan H Wilman
PURPOSE: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. MATERIALS AND METHODS: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls...
March 16, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28299468/gw-sem-a-statistical-package-to-conduct-genome-wide-structural-equation-modeling
#15
Brad Verhulst, Hermine H Maes, Michael C Neale
Improving the accuracy of phenotyping through the use of advanced psychometric tools will increase the power to find significant associations with genetic variants and expand the range of possible hypotheses that can be tested on a genome-wide scale. Multivariate methods, such as structural equation modeling (SEM), are valuable in the phenotypic analysis of psychiatric and substance use phenotypes, but these methods have not been integrated into standard genome-wide association analyses because fitting a SEM at each single nucleotide polymorphism (SNP) along the genome was hitherto considered to be too computationally demanding...
March 15, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28298218/systematic-identification-of-an-integrative-network-module-during-senescence-from-time-series-gene-expression
#16
Chihyun Park, So Jeong Yun, Sung Jin Ryu, Soyoung Lee, Young-Sam Lee, Youngmi Yoon, Sang Chul Park
BACKGROUND: Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process...
March 15, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28292982/antibiotic-capture-by-bacterial-lipocalins-uncovers-an-extracellular-mechanism-of-intrinsic-antibiotic-resistance
#17
Omar M El-Halfawy, Javier Klett, Rebecca J Ingram, Slade A Loutet, Michael E P Murphy, Sonsoles Martín-Santamaría, Miguel A Valvano
The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28292859/-18-f-fluoride-and-18-f-fluorodeoxyglucose-positron-emission-tomography-after-transient-ischemic-attack-or-minor-ischemic-stroke-case-control-study
#18
Alex T Vesey, William S A Jenkins, Agnese Irkle, Alastair Moss, Greg Sng, Rachael O Forsythe, Tim Clark, Gemma Roberts, Alison Fletcher, Christophe Lucatelli, James H F Rudd, Anthony P Davenport, Nicholas L Mills, Rustam Al-Shahi Salman, Martin Dennis, William N Whiteley, Edwin J R van Beek, Marc R Dweck, David E Newby
BACKGROUND: Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether (18)F-fluoride or (18)F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. METHODS AND RESULTS: We performed (18)F-fluoride and (18)F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma...
March 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28292312/comprehensive-discovery-of-subsample-gene-expression-components-by-information-explanation-therapeutic-implications-in-cancer
#19
Shirley Pepke, Greg Ver Steeg
BACKGROUND: De novo inference of clinically relevant gene function relationships from tumor RNA-seq remains a challenging task. Current methods typically either partition patient samples into a few subtypes or rely upon analysis of pairwise gene correlations that will miss some groups in noisy data. Leveraging higher dimensional information can be expected to increase the power to discern targetable pathways, but this is commonly thought to be an intractable computational problem. METHODS: In this work we adapt a recently developed machine learning algorithm for sensitive detection of complex gene relationships...
March 15, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28291248/a-curated-collection-of-tissue-microarray-images-and-clinical-outcome-data-of-prostate-cancer-patients
#20
Qing Zhong, Tiannan Guo, Markus Rechsteiner, Jan H Rüschoff, Niels Rupp, Christian Fankhauser, Karim Saba, Ashkan Mortezavi, Cédric Poyet, Thomas Hermanns, Yi Zhu, Holger Moch, Ruedi Aebersold, Peter J Wild
Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes...
March 14, 2017: Scientific Data
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