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Gene network inference

William Chad Young, Adrian E Raftery, Ka Yee Yeung
Inferring gene regulatory networks is an important problem in systems biology. However, these networks can be hard to infer from experimental data because of the inherent variability in biological data as well as the large number of genes involved. We propose a fast, simple method for inferring regulatory relationships between genes from knockdown experiments in the NIH LINCS dataset by calculating posterior probabilities, incorporating prior information. We show that the method is able to find previously identified edges from TRANSFAC and JASPAR and discuss the merits and limitations of this approach...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
Daniel V Guebel, Néstor V Torres
Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as "sporadic" Alzheimer. Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis)...
2016: Frontiers in Aging Neuroscience
Kevin A McGoff, Xin Guo, Anastasia Deckard, Christina M Kelliher, Adam R Leman, Lauren J Francey, John B Hogenesch, Steven B Haase, John L Harer
We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, sizes, and degrees of complexity. Moreover, we demonstrate its ability to incorporate biological prior information and make informative predictions on a well-characterized in vivo system using data from budding yeast that have been synchronized in the cell cycle...
October 19, 2016: Genome Biology
Daifeng Wang, Fei He, Sergei Maslov, Mark Gerstein
Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution...
October 2016: PLoS Computational Biology
Nídia Cangi, Jonathan L Gordon, Laure Bournez, Valérie Pinarello, Rosalie Aprelon, Karine Huber, Thierry Lefrançois, Luís Neves, Damien F Meyer, Nathalie Vachiéry
The disease, Heartwater, caused by the Anaplasmataceae E. ruminantium, represents a major problem for tropical livestock and wild ruminants. Up to now, no effective vaccine has been available due to a limited cross protection of vaccinal strains on field strains and a high genetic diversity of Ehrlichia ruminantium within geographical locations. To address this issue, we inferred the genetic diversity and population structure of 194 E. ruminantium isolates circulating worldwide using Multilocus Sequence Typing based on lipA, lipB, secY, sodB, and sucA genes...
2016: Frontiers in Cellular and Infection Microbiology
Jie Zhou, Pianyu Zhong, Tinghui Zhang
Determination of sequence similarity is one of the major steps in computational phylogenetic studies. One of the major tasks of computational biologists is to develop novel mathematical descriptors for similarity analysis. DNA clustering is an important technology that automatically identifies inherent relationships among large-scale DNA sequences. The comparison between the DNA sequences of different species helps determine phylogenetic relationships among species. Alignment-free approaches have continuously gained interest in various sequence analysis applications such as phylogenetic inference and metagenomic classification/clustering, particularly for large-scale sequence datasets...
2016: Evolutionary Bioinformatics Online
Lianshuo Li, Zicheng Wang, Peng He, Shining Ma, Jie Du, Rui Jiang
Although networks of microbial species have been widely used in the analysis of 16S rRNA sequencing data of a microbiome, the construction and analysis of a complete microbial gene network is in general problematic because of the large number of microbial genes in metagenomics studies. To overcome this limitation, we propose to map microbial genes to functional units, including KEGG orthologous groups and the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) orthologous groups, to enable the construction and analysis of a microbial functional network...
October 13, 2016: Genomics, Proteomics & Bioinformatics
Wenqing Fu, Sharon R Browning, Brian L Browning, Joshua M Akey
Identifying and characterizing genomic regions that are shared identical by descent (IBD) among individuals can yield insight into population history, facilitate the identification of adaptively evolving loci, and be an important tool in disease gene mapping. Although increasingly large collections of exome sequences have been generated, it is challenging to detect IBD segments in exomes, precluding many potentially informative downstream analyses. Here, we describe an approach, ExIBD, to robustly detect IBD segments in exome-sequencing data, rigorously evaluate its performance, and apply this method to high-coverage exomes from 6,515 European and African Americans...
October 6, 2016: American Journal of Human Genetics
Anatoly Yambartsev, Michael A Perlin, Yevgeniy Kovchegov, Natalia Shulzhenko, Karina L Mine, Xiaoxi Dong, Andrey Morgun
BACKGROUND: Gene covariation networks are commonly used to study biological processes. The inference of gene covariation networks from observational data can be challenging, especially considering the large number of players involved and the small number of biological replicates available for analysis. RESULTS: We propose a new statistical method for estimating the number of erroneous edges in reconstructed networks that strongly enhances commonly used inference approaches...
October 13, 2016: Biology Direct
Hussein A Hejase, Kevin J Liu
BACKGROUND: Branching events in phylogenetic trees reflect bifurcating and/or multifurcating speciation and splitting events. In the presence of gene flow, a phylogeny cannot be described by a tree but is instead a directed acyclic graph known as a phylogenetic network. Both phylogenetic trees and networks are typically reconstructed using computational analysis of multi-locus sequence data. The advent of high-throughput sequencing technologies has brought about two main scalability challenges: (1) dataset size in terms of the number of taxa and (2) the evolutionary divergence of the taxa in a study...
October 13, 2016: BMC Bioinformatics
Sabine Gollner, Heiko Stuckas, Terue C Kihara, Stefan Laurent, Sahar Kodami, Pedro Martinez Arbizu
Communities in spatially fragmented deep-sea hydrothermal vents rich in polymetallic sulfides could soon face major disturbance events due to deep-sea mineral mining, such that unraveling patterns of gene flow between hydrothermal vent populations will be an important step in the development of conservation policies. Indeed, the time required by deep-sea populations to recover following habitat perturbations depends both on the direction of gene flow and the number of migrants available for re-colonization after disturbance...
2016: PloS One
Evi Berchtold, Gergely Csaba, Ralf Zimmer
Several methods predict activity changes of transcription factors (TFs) from a given regulatory network and measured expression data. But available gene regulatory networks are incomplete and contain many condition-dependent regulations that are not relevant for the specific expression measurement. It is not known which combination of active TFs is needed to cause a change in the expression of a target gene. A method to systematically evaluate the inferred activity changes is missing. We present such an evaluation strategy that indicates for how many target genes the observed expression changes can be explained by a given set of active TFs...
2016: PloS One
Michael Seifert, Betty Friedrich, Andreas Beyer
It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis...
October 3, 2016: Genome Biology
Chien-Hung Huang, Jin-Shuei Ciou, Shun-Tsung Chen, Victor C Kok, Yi Chung, Jeffrey J P Tsai, Nilubon Kurubanjerdjit, Chi-Ying F Huang, Ka-Lok Ng
BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMC) is a major cause of cardiovascular diseases (CVDs). Many studies suggest that vascular injury triggers VSMC dedifferentiation, which results in VSMC changes from a contractile to a synthetic phenotype; however, the underlying molecular mechanisms are still unclear. METHODS: In this study, we examined how VSMC responds under mechanical stress by using time-course microarray data. A three-phase study was proposed to investigate the stress-induced differentially expressed genes (DEGs) in VSMC...
2016: PeerJ
Kewei Feng, Fuyan Liu, Jinwei Zou, Guangwei Xing, Pingchuan Deng, Weining Song, Wei Tong, Xiaojun Nie
Mitogen-activated protein kinase (MAPK) cascades are the conserved and universal signal transduction modules in all eukaryotes, which play the vital roles in plant growth, development, and in response to multiple stresses. In this study, we used bioinformatics methods to identify 86 MAPKKK protein encoded by 73 MAPKKK genes in Brachypodium. Phylogenetic analysis of MAPKKK family from Arabidopsis, rice, and Brachypodium has classified them into three subfamilies, of which 28 belonged to MEKK, 52 to Raf, and 6 to ZIK subfamily, respectively...
2016: Frontiers in Plant Science
H J Yu, Y Kai, J-K Kim
This paper presents preliminary data on the genetic diversity and population structure of Hyporhamphus sajori by analysing a 510 bp sequence in the mitochondrial DNA (mtDNA) control region and eight polymorphic microsatellite DNA loci. The H. sajori individuals from different locations were indistinguishable from one another based on mtDNA variation, as demonstrated with a neighbour-joining tree and minimum spanning network analysis. Low level of genetic diversity and the absence of population structure in H...
September 29, 2016: Journal of Fish Biology
Stephen Starko Francis, Mateusz M Plucinski, Amelia D Wallace, Lee W Riley
Social network structure is a fundamental determinant of human health, from infectious to chronic diseases. However, quantitative and unbiased approaches to measuring social network structure are lacking. We hypothesized that genetic relatedness of oral commensal bacteria could be used to infer social contact between humans, just as genetic relatedness of pathogens can be used to determine transmission chains of pathogens. We used a traditional, questionnaire survey-based method to characterize the contact network of the School of Public Health at a large research university...
2016: PloS One
Zhaowu Ma, Teng Liu, Wei Huang, Hui Liu, Hong-Mei Zhang, Qiubai Li, Zhichao Chen, An-Yuan Guo
MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher's exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo...
September 24, 2016: Oncotarget
Ye Sun, Yanshu Li, Carlos Fabián Vargas-Mendoza, Faguo Wang, Fuwu Xing
Diversification between islands and ecological radiation within islands are postulated to have occurred in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands. In this study, the biogeographical pattern of 11 species of subsect. Macaronesicae and the genetic differentiation among five species were investigated to distinguish the potential mode and mechanism of diversification and speciation. The biogeographical patterns and genetic structure were examined using statistical dispersal-vicariance analysis, Bayesian phylogenetic analysis, reduced median-joining haplotype network analysis, and discriminant analysis of principal components...
September 29, 2016: Scientific Reports
Davide S Sardina, Salvatore Alaimo, Alfredo Ferro, Alfredo Pulvirenti, Rosalba Giugno
Posttranscriptional cross talk and communication between genes mediated by microRNA response element (MREs) yield large regulatory competing endogenous RNA (ceRNA) networks. Their inference may improve the understanding of pathologies and shed new light on biological mechanisms. A variety of RNA: messenger RNA, transcribed pseudogenes, noncoding RNA, circular RNA and proteins related to RNA-induced silencing complex complex interacting with RNA transfer and ribosomal RNA have been experimentally proved to be ceRNAs...
September 26, 2016: Briefings in Bioinformatics
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