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Gene network inference

Heeju Noh, Jason E Shoemaker, Rudiyanto Gunawan
Genome-wide transcriptional profiling provides a global view of cellular state and how this state changes under different treatments (e.g. drugs) or conditions (e.g. healthy and diseased). Here, we present ProTINA (Protein Target Inference by Network Analysis), a network perturbation analysis method for inferring protein targets of compounds from gene transcriptional profiles. ProTINA uses a dynamic model of the cell-type specific protein-gene transcriptional regulation to infer network perturbations from steady state and time-series differential gene expression profiles...
January 9, 2018: Nucleic Acids Research
Daniel Trejo Banos, Pauline Trébulle, Mohamed Elati
BACKGROUND: Genome-scale metabolic models provide an opportunity for rational approaches to studies of the different reactions taking place inside the cell. The integration of these models with gene regulatory networks is a hot topic in systems biology. The methods developed to date focus mostly on resolving the metabolic elements and use fairly straightforward approaches to assess the impact of genome expression on the metabolic phenotype. RESULTS: We present here a method for integrating the reverse engineering of gene regulatory networks into these metabolic models...
December 21, 2017: BMC Systems Biology
Jiafan Zhu, Dingqiao Wen, Yun Yu, Heidi M Meudt, Luay Nakhleh
Phylogenetic networks are rooted, directed, acyclic graphs that model reticulate evolutionary histories. Recently, statistical methods were devised for inferring such networks from either gene tree estimates or the sequence alignments of multiple unlinked loci. Bi-allelic markers, most notably single nucleotide polymorphisms (SNPs) and amplified fragment length polymorphisms (AFLPs), provide a powerful source of genome-wide data. In a recent paper, a method called SNAPP was introduced for statistical inference of species trees from unlinked bi-allelic markers...
January 10, 2018: PLoS Computational Biology
C F Blum, N Heramvand, A S Khonsari, M Kollmann
Generating a comprehensive map of molecular interactions in living cells is difficult and great efforts are undertaken to infer molecular interactions from large-scale perturbation experiments. Here, we develop the analytical and numerical tools to quantify the fundamental limits for inferring transcriptional networks from gene knockout screens and introduce a network inference method that is unbiased with respect to measurement noise and scalable to large network sizes. We show that network asymmetry, knockout coverage and measurement noise are central determinants that limit prediction accuracy, whereas the knowledge about gene-specific variability among biological replicates can be used to eliminate noise-sensitive nodes and thereby boost the performance of network inference algorithms...
January 9, 2018: Nature Communications
Valentin Voillet, Magali San Cristobal, Marie-Christine Pere, Yvon Billon, Laurianne Canario, Laurence Liaubet, Louis Lefaucheur
BACKGROUND: In pigs, the perinatal period is the most critical time for survival. Piglet maturation, which occurs at the end of gestation, leads to a state of full development after birth. Maturity is thus an important determinant of early survival. Skeletal muscle plays a key role in adaptation to extra-uterine life, e.g. motor function and thermoregulation. Progeny from two breeds with extreme neonatal mortality rates were analyzed at 90 and 110 days of gestation (dg). The Large White breed is a highly selected breed for lean growth with a high rate of mortality at birth, whereas the Chinese Meishan breed is fatter and more robust and has a low mortality rate...
January 8, 2018: Molecular & Cellular Proteomics: MCP
Purushottam D Dixit, Jason Wagoner, Corey Weistuch, Steve Pressé, Kingshuk Ghosh, Ken A Dill
We review here Maximum Caliber (Max Cal), a general variational principle for inferring distributions of paths in dynamical processes and networks. Max Cal is to dynamical trajectories what the principle of maximum entropy is to equilibrium states or stationary populations. In Max Cal, you maximize a path entropy over all possible pathways, subject to dynamical constraints, in order to predict relative path weights. Many well-known relationships of non-equilibrium statistical physics-such as the Green-Kubo fluctuation-dissipation relations, Onsager's reciprocal relations, and Prigogine's minimum entropy production-are limited to near-equilibrium processes...
January 7, 2018: Journal of Chemical Physics
Dan Li, William Yang, Jialing Zhang, Jack Y Yang, Renchu Guan, Mary Qu Yang
Lung cancer is the second most commonly diagnosed carcinoma and is the leading cause of cancer death. Although significant progress has been made towards its understanding and treatment, unraveling the complexities of lung cancer is still hampered by a lack of comprehensive knowledge on the mechanisms underlying the disease. High-throughput and multidimensional genomic data have shed new light on cancer biology. In this study, we developed a network-based approach integrating somatic mutations, the transcriptome, DNA methylation, and protein-DNA interactions to reveal the key regulators in lung adenocarcinoma (LUAD)...
January 5, 2018: Genes
Hamid Beiki, Abbas Pakdel, Ardeshir Nejati Javaremi, Ali Masoudi-Nejad, James M Reecy
BACKGROUND: Weighted Gene Co-expression Network analysis, a powerful technique used to extract co-expressed gene pattern from mRNA expression data, was constructed to infer common immune strategies used by cattle in response to five different bacterial species (Escherichia coli, Mycobacterium avium, Mycobacterium bovis, Salmonella and Staphylococcus aureus) and a protozoa (Trypanosoma Congolense) using 604 publicly available gene expression microarrays from 12 cattle infection experiments...
January 5, 2018: BMC Immunology
Mengmeng Wu, Zhixiang Lin, Shining Ma, Ting Chen, Rui Jiang, Wing Hung Wong
Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies...
December 29, 2017: Journal of Molecular Cell Biology
Zhen Tian, Maozu Guo, Chunyu Wang, LinLin Xing, Lei Wang, Yin Zhang
BACKGROUND: Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale...
September 20, 2017: Journal of Biomedical Semantics
Z Mozduri, M R Bakhtiarizadeh, A Salehi
Negative energy balance (NEB) is an altered metabolic state in modern high-yielding dairy cows. This metabolic state occurs in the early postpartum period when energy demands for milk production and maintenance exceed that of energy intake. Negative energy balance or poor adaptation to this metabolic state has important effects on the liver and can lead to metabolic disorders and reduced fertility. The roles of regulatory factors, including transcription factors (TFs) and micro RNAs (miRNAs) have often been separately studied for evaluating of NEB...
December 28, 2017: Animal: An International Journal of Animal Bioscience
Alyssa Imbert, Armand Valsesia, Caroline Le Gall, Claudia Armenise, Gregory Lefebvre, Pierre-Antoine Gourraud, Nathalie Viguerie, Nathalie Villa-Vialaneix
Motivation: Network inference provides a global view of the relations existing between gene expression in a given transcriptomic experiment (often only for a restricted list of chosen genes). However, it is still a challenging problem: even if the cost of sequencing techniques has decreased over the last years, the number of samples in a given experiment is still (very) small compared to the number of genes. Results: We propose a method to increase the reliability of the inference when RNA-seq expression data have been measured together with an auxiliary dataset that can provide external information on gene expression similarity between samples...
December 21, 2017: Bioinformatics
Xi Chen, Jinghua Gu, Xiao Wang, Jin-Gyoung Jung, Tian-Li Wang, Leena Hilakivi-Clarke, Robert Clarke, Jianhua Xuan
Motivation: NGS techniques have been widely applied in genetic and epigenetic studies. Multiple ChIP-seq and RNA-seq profiles can now be jointly used to infer functional regulatory networks (FRNs). However, existing methods suffer from either oversimplified assumption on transcription factor (TF) regulation or slow convergence of sampling for FRN inference from large-scale ChIP-seq and time-course RNA-seq data. Results: We developed an efficient Bayesian integration method (CRNET) for FRN inference using a two-stage Gibbs sampler to estimate iteratively hidden TF activities and the posterior probabilities of binding events...
December 21, 2017: Bioinformatics
Su-Yi Loh, Thomas Jahans-Price, Michael P Greenwood, Mingkwan Greenwood, See-Ziau Hoe, Agnieszka Konopacka, Colin Campbell, David Murphy, Charles C T Hindmarch
The supraoptic nucleus (SON) is a group of neurons in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised graphical lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions...
November 2017: ENeuro
Yang Liu, Perry Palmedo, Qing Ye, Bonnie Berger, Jian Peng
While genes are defined by sequence, in biological systems a protein's function is largely determined by its three-dimensional structure. Evolutionary information embedded within multiple sequence alignments provides a rich source of data for inferring structural constraints on macromolecules. Still, many proteins of interest lack sufficient numbers of related sequences, leading to noisy, error-prone residue-residue contact predictions. Here we introduce DeepContact, a convolutional neural network (CNN)-based approach that discovers co-evolutionary motifs and leverages these patterns to enable accurate inference of contact probabilities, particularly when few related sequences are available...
December 19, 2017: Cell Systems
Zhijun Wu, Xiuxiu Su, Haihui Sheng, Yanjia Chen, Xiang Gao, Le Bao, Wei Jin
BACKGROUND AND AIMS: Identifying gene-environment interaction in the context of multiple environmental factors has been a challenging task. We aimed to use conditional inference tree (CTREE) to strata myocardial infarction (MI) risk synthesizing information from both genetic and environmental factors. METHODS: We conducted a case-control study including 1440 Chinese men (730 MI patients and 710 controls). We first calculated a weighted genetic risk score (GRS) by combining 25 single nucleotide polymorphisms (SNPs) that had been identified to be associated with coronary artery diseases in previous genome wide association studies...
December 16, 2017: Archives of Medical Research
Ivailo Alexiev, Alessandra Lo Presti, Reneta Dimitrova, Brian Thomas Foley, Anna Gancheva, Asya Kostadinova, Lora Nikolova, Silvia Angeletti, Eleonora Cella, Ivaylo Elenkov, Mariana Stoycheva, Daniela Nikolova, Tsetsa Doychinova, Liliya Pekova, Massimo Ciccozzi
Human Immunodeficiency Virus (HIV) was originally introduced in Bulgaria through heterosexual transmission (HET) and later transferred to other vulnerable groups along with numerous more recent introductions from outside Bulgaria. To define the diversity, origins and dynamics of the HIV-1 subtypes prevalent in HET population in Bulgaria we applied phylogenetic and phylodynamic analyses using polymerase (pol) sequences from HET individuals to infer the spatiotemporal evolutionary history of the HIV-1 epidemic in this population in Bulgaria...
December 19, 2017: AIDS Research and Human Retroviruses
Lei Chen, Yu-Hang Zhang, JiaRui Li, ShaoPeng Wang, YunHua Zhang, Tao Huang, Yu-Dong Cai
The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases...
December 18, 2017: Genes
Julian Daniel Schwab, Lea Siegle, Silke Daniela Kühlwein, Michael Kühl, Hans Armin Kestler
Biological pathways are thought to be robust against a variety of internal and external perturbations. Fail-safe mechanisms allow for compensation of perturbations to maintain the characteristic function of a pathway. Pathways can undergo changes during aging, which may lead to changes in their stability. Less stable or less robust pathways may be consequential to or increase the susceptibility of the development of diseases. Among others, NF- κ B signaling is a crucial pathway in the process of aging. The NF- κ B system is involved in the immune response and dealing with various internal and external stresses...
December 18, 2017: Biology
Neelam Redekar, Guillaume Pilot, Victor Raboy, Song Li, M A Saghai Maroof
A dominant loss of function mutation in myo-inositol phosphate synthase (MIPS) gene and recessive loss of function mutations in two multidrug resistant protein type-ABC transporter genes not only reduce the seed phytic acid levels in soybean, but also affect the pathways associated with seed development, ultimately resulting in low emergence. To understand the regulatory mechanisms and identify key genes that intervene in the seed development process in low phytic acid crops, we performed computational inference of gene regulatory networks in low and normal phytic acid soybeans using a time course transcriptomic data and multiple network inference algorithms...
2017: Frontiers in Plant Science
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