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https://www.readbyqxmd.com/read/28108552/predicted-residual-error-sum-of-squares-of-mixed-models-an-application-to-genomic-prediction
#1
Shizhong Xu
Genomic prediction is a statistical method to predict phenotypes of polygenic traits using high throughput genomic data. Most diseases and behaviors in human and animals are polygenic traits. The majority of agronomic traits in crops are also polygenic. Accurate prediction of these traits can help medical professionals diagnose acute diseases and breeders to increase food products, and therefore, significantly contribute to human health and global food security. The best linear unbiased prediction (BLUP) is an important tool to analyze high throughput genomic data for prediction...
January 20, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28108314/mirna-638-promotes-autophagy-and-malignant-phenotypes-of-cancer-cells-via-directly-suppressing-dact3
#2
Yanli Ren, Yujie Chen, Xue Liang, Yan Lu, Wenting Pan, Ming Yang
Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promote cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues...
January 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28107392/upon-accounting-for-the-impact-of-isoenzyme-loss-gene-deletion-costs-anticorrelate-with-their-evolutionary-rates
#3
Christopher Jacobs, Luke Lambourne, Yu Xia, Daniel Segrè
System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution...
2017: PloS One
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#4
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105934/charm-discovery-of-combinatorial-chromatin-modification-patterns-in-hepatitis-b-virus-x-transformed-mouse-liver-cancer-using-association-rule-mining
#5
Sung Hee Park, Sun-Min Lee, Young-Joon Kim, Sangsoo Kim
BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103880/the-use-of-genome-scale-metabolic-network-reconstruction-to-predict-fluxes-and-equilibrium-composition-of-n-fixing-versus-c-fixing-cells-in-a-diazotrophic-cyanobacterium-trichodesmium-erythraeum
#6
Joseph J Gardner, Nanette R Boyle
BACKGROUND: Computational, genome based predictions of organism phenotypes has enhanced the ability to investigate the biological phenomena that help organisms survive and respond to their environments. In this study, we have created the first genome-scale metabolic network reconstruction of the nitrogen fixing cyanobacterium T. erythraeum and used genome-scale modeling approaches to investigate carbon and nitrogen fluxes as well as growth and equilibrium population composition. RESULTS: We created a genome-scale reconstruction of T...
January 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28103804/inactivity-periods-and-postural-change-speed-can-explain-atypical-postural-change-patterns-of-caenorhabditis-elegans-mutants
#7
Tsukasa Fukunaga, Wataru Iwasaki
BACKGROUND: With rapid advances in genome sequencing and editing technologies, systematic and quantitative analysis of animal behavior is expected to be another key to facilitating data-driven behavioral genetics. The nematode Caenorhabditis elegans is a model organism in this field. Several video-tracking systems are available for automatically recording behavioral data for the nematode, but computational methods for analyzing these data are still under development. RESULTS: In this study, we applied the Gaussian mixture model-based binning method to time-series postural data for 322 C...
January 19, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28096084/timesvector-a-vectorized-clustering-approach-to-the-analysis-of-time-series-transcriptome-data-from-multiple-phenotypes
#8
Inuk Jung, Kyuri Jo, Hyejin Kang, Hongryul Ahn, Youngjae Yu, Sun Kim
MOTIVATION: Identifying biologically meaningful gene expression patterns from time series gene expression data is important to understand the underlying biological mechanisms. To identify significantly perturbed gene sets between different phenotypes, analysis of time series transcriptome data requires consideration of time and sample dimensions. Thus, the analysis of such time series data seeks to search gene sets that exhibit similar or different expression patterns between two or more sample conditions, constituting the three-dimensional data, i...
January 17, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28095178/current-trends-in-multidrug-optimization
#9
Andrea Weiss, Patrycja Nowak-Sliwinska
The identification of effective and long-lasting cancer therapies still remains elusive, partially due to patient and tumor heterogeneity, acquired drug resistance, and single-drug dose-limiting toxicities. The use of drug combinations may help to overcome some limitations of current cancer therapies by challenging the robustness and redundancy of biological processes. However, effective drug combination optimization requires the careful consideration of numerous parameters. The complexity of this optimization problem is clearly nontrivial and likely requires the assistance of advanced heuristic optimization techniques...
December 1, 2016: Journal of Laboratory Automation
https://www.readbyqxmd.com/read/28094442/identifying-niche-mediated-regulatory-factors-of-stem-cell-phenotypic-state-a-systems-biology-approach
#10
Srikanth Ravichandran, Antonio Del Sol
Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and non-linear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants)...
January 17, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28093065/comparison-of-alternative-approaches-to-single-trait-genomic-prediction-using-genotyped-and-non-genotyped-hanwoo-beef-cattle
#11
Joonho Lee, Hao Cheng, Dorian Garrick, Bruce Golden, Jack Dekkers, Kyungdo Park, Deukhwan Lee, Rohan Fernando
BACKGROUND: Genomic predictions from BayesA and BayesB use training data that include animals with both phenotypes and genotypes. Single-step methodologies allow additional information from non-genotyped relatives to be included in the analysis. The single-step genomic best linear unbiased prediction (SSGBLUP) method uses a relationship matrix computed from marker and pedigree information, in which missing genotypes are imputed implicitly. Single-step Bayesian regression (SSBR) extends SSGBLUP to BayesB-like models using explicitly imputed genotypes for non-genotyped individuals...
January 4, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28092658/mutation-effects-predicted-from-sequence-co-variation
#12
Thomas A Hopf, John B Ingraham, Frank J Poelwijk, Charlotta P I Schärfe, Michael Springer, Chris Sander, Debora S Marks
Many high-throughput experimental technologies have been developed to assess the effects of large numbers of mutations (variation) on phenotypes. However, designing functional assays for these methods is challenging, and systematic testing of all combinations is impossible, so robust methods to predict the effects of genetic variation are needed. Most prediction methods exploit evolutionary sequence conservation but do not consider the interdependencies of residues or bases. We present EVmutation, an unsupervised statistical method for predicting the effects of mutations that explicitly captures residue dependencies between positions...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092388/exploration-and-analysis-of-drug-modes-of-action-through-feature-integration
#13
Mingyuan Xin, Jun Fan, Mingyao Liu, Zhenran Jiang
Identifying drug modes of action (MoA) is of paramount importance for having a good grasp of drug indications in clinical tests. Anticipating MoA can help to discover new uses for approved drugs. Here we first used a drug-set enrichment analysis method to discover significant biological activities in every mode of action category. Then, we proposed a new computational model, a probability ensemble approach based on Bayesian network theory, which integrated chemical, therapeutic, genomic and phenotypic properties of over a thousand of FDA approved drugs to assist with the prediction of MoA...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28090778/three-novel-spectrin-variants-in-jaundiced-neonates
#14
Robert D Christensen, Archana M Agarwal, Hassan M Yaish, N Scott Reading, Elizabeth A O'Brien, Josef T Prchal
Various mutations in the genes encoding alpha spectrin (SPTA1) or beta spectrin (SPTB) are known to cause erythrocyte membrane disorders, sometimes associated with severe neonatal jaundice and anemia. We used a next-generation sequencing panel to evaluate 3 unrelated neonates who had puzzling cases of nonimmune hemolytic jaundice. In each case, we identified novel mutations in either SPTA1 or SPTB. Correlating erythrocyte morphology, clinical course, and computational analysis, we submit that each of the 3 variants is a probable pathogenic cause of the hereditary hemolytic conditions in these patients...
January 1, 2017: Clinical Pediatrics
https://www.readbyqxmd.com/read/28090405/transcriptomic-analysis-of-diplomonad-parasites-reveals-a-trans-spliced-intron-in-a-helicase-gene-in-giardia
#15
Scott William Roy
BACKGROUND: The mechanisms by which DNA sequences are expressed is the central preoccupation of molecular genetics. Recently, ourselves and others reported that in the diplomonad protist Giardia lamblia, the coding regions of several mRNAs are produced by ligation of independent RNA species expressed from distinct genomic loci. Such trans-splicing of introns was found to affect nearly as many genes in this organism as does classical cis-splicing of introns. These findings raised questions about the incidence of intron trans-splicing both across the G...
2017: PeerJ
https://www.readbyqxmd.com/read/28089131/transcriptome-wide-identification-and-functional-investigation-of-circular-rna-in-the-teleost-large-yellow-croaker-larimichthys-crocea
#16
Shuangbin Xu, Shijun Xiao, Changliang Qiu, Zhiyong Wang
Circular RNA (circRNA) was first reported over thirty years ago. With the development of high-throughput sequencing technologies, circRNA has been identified in an increasing number of species. However, few studies on circRNA have been reported in teleost fish. Accumulating transcriptome and phenotype data enable us to probe the biological functions of circRNA in fish species. Here, we report the identification of circRNAs from RNA sequencing (RNA-seq) data in large yellow croaker (Larimichthys crocea), a commercially important marine fish in China and East Asia...
January 6, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28088216/immunohistochemical-features-of-giant-cell-ependymoma-of-the-filum-terminale-with-unusual-clinical-and-radiological-presentation
#17
Fernando Candanedo-Gonzalez, Cindy Sharon Ortiz-Arce, Samuel Rosales-Perez, Ana Lilia Remirez-Castellanos, Candelaria Cordova-Uscanga, Armando Gamboa-Dominguez
BACKGROUND: Giant cell ependymoma of the filum terminale is a rare variant, generally manifested as a well-circunscribed intradural mass with an indolent biological behavior. CASE PRESENTATION: We describe the case of a 48-year-old Mexican female who non-relevant past medical history, that developed a GCE of the filum terminale. Magnetic resonance imaging and computed tomography revealed the presence of an intra-axial tumor extending from L3 to L5 with extra-medullary invasion...
January 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28087116/application-of-whole-exome-sequencing-in-elucidating-the-phenotype-and-genotype-spectrum-of-junctional-epidermolysis-bullosa-a-preliminary-experience-of-a-tertiary-care-centre-in-india
#18
Vamsi K Yenamandra, Shamsudheen K Vellarikkal, Manoj Kumar, Madhumita R Chowdhury, Rijith Jayarajan, Ankit Verma, Vinod Scaria, Sridhar Sivasubbu, Subrata B Ray, Amit K Dinda, Madhulika Kabra, Punit Kaur, Vinod K Sharma, Gomathy Sethuraman
BACKGROUND: Junctional epidermolysis bullosa (JEB) is a diverse group of genodermatoses associated with extreme skin fragility. Despite several well-characterized genetic studies, molecular diagnosis of this heterogeneous group is still challenging. Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing (WES) as a fast and efficient diagnostic strategy in several genodermatoses. OBJECTIVE: In view of the scarcity and need of molecular studies for JEB in India, we sought to explore the potential of WES in understanding the mutational spectrum of this rare, in certain subtypes lethal, sub-group of EB...
December 29, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28081260/comparative-genome-sequencing-reveals-within-host-genetic-changes-in-neisseria-meningitidis-during-invasive-disease
#19
Johanna Klughammer, Marcus Dittrich, Jochen Blom, Vera Mitesser, Ulrich Vogel, Matthias Frosch, Alexander Goesmann, Tobias Müller, Christoph Schoen
Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation...
2017: PloS One
https://www.readbyqxmd.com/read/28081208/optimizing-training-population-size-and-genotyping-strategy-for-genomic-prediction-using-association-study-results-and-pedigree-information-a-case-of-study-in-advanced-wheat-breeding-lines
#20
Fabio Cericola, Ahmed Jahoor, Jihad Orabi, Jeppe R Andersen, Luc L Janss, Just Jensen
Wheat breeding programs generate a large amount of variation which cannot be completely explored because of limited phenotyping throughput. Genomic prediction (GP) has been proposed as a new tool which provides breeding values estimations without the need of phenotyping all the material produced but only a subset of it named training population (TP). However, genotyping of all the accessions under analysis is needed and, therefore, optimizing TP dimension and genotyping strategy is pivotal to implement GP in commercial breeding schemes...
2017: PloS One
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