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Gene network inference

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https://www.readbyqxmd.com/read/28812537/leveraging-network-analytics-to-infer-patient-syndrome-and-identify-causal-genes-in-rare-disease-cases
#1
Andreas Krämer, Sohela Shah, Robert Anthony Rebres, Susan Tang, Daniel Rene Richards
BACKGROUND: Next-generation sequencing is widely used to identify disease-causing variants in patients with rare genetic disorders. Identifying those variants from whole-genome or exome data can be both scientifically challenging and time consuming. A significant amount of time is spent on variant annotation, and interpretation. Fully or partly automated solutions are therefore needed to streamline and scale this process. RESULTS: We describe Phenotype Driven Ranking (PDR), an algorithm integrated into Ingenuity Variant Analysis, that uses observed patient phenotypes to prioritize diseases and genes in order to expedite causal-variant discovery...
August 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28811334/argonaute-8-ago8-mediates-the-elicitation-of-primary-defense-against-herbivory
#2
Maitree Pradhan, Priyanka Pandey, Klaus Gase, Murali Shraff, Ravi K Singh, Avinash Sethi, Ian T Baldwin, Shree P Pandey
In Nicotiana attenuata, specific RNA directed RNA polymerase (RdR1) and the Dicer-like proteins (DCL3 and 4) are recruited during herbivore attack to mediate the regulation of defense responses. However, the identity and role(s) of Argonautes (AGOs) involved in herbivory remains unknown. Of the 11 AGOs in the N. attenuata genome, we silenced the expression of 10. Plants silenced in NaAGO8 expression grew normally but were highly susceptible to herbivore attack. Larvae of the Manduca sexta grew faster when consuming irAGO8 plants, but did not differ from WT when consuming plants silenced in AGO1 (a, b and c), AGO2, AGO4 (a and b), AGO7, or AGO10 expression...
August 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28809429/dissection-of-the-module-network-implementation-lemontree-enhancements-towards-applications-in-metagenomics-and-translation-in-autoimmune-maladies
#3
Youtao Lu, Xiaoyuan Zhou, Christine Nardini
Under the current deluge of omics, module networks distinctively emerge as methods capable of not only identifying inherently coherent groups (modules), thus reducing dimensionality, but also hypothesizing cause-effect relationships between modules and their regulators. Module networks were first designed in the transcriptomic era and further exploited in the multi-omic context to assess (for example) miRNA regulation of gene expression. Despite a number of available implementations, expansion of module networks to other omics is constrained by a limited characterization of the solutions' (modules plus regulators) accuracy and stability - an immediate need for the better characterization of molecular biology complexity in silico...
August 15, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28808032/mechanical-constraint-from-growing-jaw-facilitates-mammalian-dental-diversity
#4
Elodie Renvoisé, Kathryn D Kavanagh, Vincent Lazzari, Teemu J Häkkinen, Ritva Rice, Sophie Pantalacci, Isaac Salazar-Ciudad, Jukka Jernvall
Much of the basic information about individual organ development comes from studies using model species. Whereas conservation of gene regulatory networks across higher taxa supports generalizations made from a limited number of species, generality of mechanistic inferences remains to be tested in tissue culture systems. Here, using mammalian tooth explants cultured in isolation, we investigate self-regulation of patterning by comparing developing molars of the mouse, the model species of mammalian research, and the bank vole...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807930/transcriptome-association-identifies-regulators-of-wheat-spike-architecture
#5
Yuange Wang, Haopeng Yu, Caihuan Tian, Muhammad Sajjad, Caixia Gao, Yiping Tong, Xiangfeng Wang, Yuling Jiao
The architecture of wheat inflorescence and its complexity is among the most important agronomic traits that influence yield. For example, wheat spikes vary considerably in the number of spikelets, which are specialized reproductive branches, and the number of florets, which are spikelet branches that produce seeds. The large and repetitive nature of the three homologous and highly similar subgenomes of wheat has impeded attempts at using genetic approaches to uncover beneficial alleles that can be utilized for yield improvement...
August 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28806280/integrated-analysis-of-biopsies-from-inflammatory-bowel-disease-patients-identifies-saa1-as-a-link-between-mucosal-microbes-with-th17-and-th22-cells
#6
Mei San Tang, Rowann Bowcutt, Jacqueline M Leung, Martin J Wolff, Uma M Gundra, David Hudesman, Lisa B Malter, Michael A Poles, Lea Ann Chen, Zhiheng Pei, Antonio G Neto, Wasif M Abidi, Thomas Ullman, Lloyd Mayer, Richard A Bonneau, Ilseung Cho, Pʼng Loke
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD...
August 9, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28804242/immuno-oncology-integrative-networks-elucidating-the-influences-of-osteosarcoma-phenotypes
#7
REVIEW
Ankush Sharma, Enrico Capobianco
In vivo and in vitro functional phenotyping characterization was recently obtained with reference to an experimental pan-cancer study of 22 osteosarcoma (OS) cell lines. Here, differentially expressed gene (DEG) profiles were recomputed from the publicly available data to conduct network inference on the immune system regulatory activity across the characterized OS phenotypes. Based on such DEG profiles, and for each phenotype that was analyzed, we obtained coexpression networks and bio-annotations for them...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28802227/anti-inflammatory-effects-of-shufengjiedu-capsule-for-upper-respiratory-infection-via-the-erk-pathway
#8
Yanmei Li, Nianwei Chang, Yanqi Han, Mengge Zhou, Jie Gao, Yuanyuan Hou, Min Jiang, Tiejun Zhang, Gang Bai
BACKGROUND: Shufengjiedu Capsule (SFJD) is a type of Chinese traditional medicine compound for the treatment of acute upper respiratory tract infection. The present work aims to decipher the mechanism of SFJD. METHODS: In this study, we used target prediction and RNA sequence (RNA-Seq) based on transcriptome analysis to clarify the inflammation-eliminating mechanism of SFJD. Firstly, Pseudomonas aeruginosa (PAK) was used to induce acute lung injury in KM mice. After being treated by SFJD, the differently expressed genes were analyzed by RNA-Seq...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28800327/analytical-strategy-to-prioritize-alzheimer-s-disease-candidate-genes-in-gene-regulatory-networks-using-public-expression-data
#9
Shweta Bagewadi Kawalia, Tamara Raschka, Mufassra Naz, Ricardo de Matos Simoes, Philipp Senger, Martin Hofmann-Apitius
Alzheimer's disease (AD) progressively destroys cognitive abilities in the aging population with tremendous effects on memory. Despite recent progress in understanding the underlying mechanisms, high drug attrition rates have put a question mark behind our knowledge about its etiology. Re-evaluation of past studies could help us to elucidate molecular-level details of this disease. Several methods to infer such networks exist, but most of them do not elaborate on context specificity and completeness of the generated networks, missing out on lesser-known candidates...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28797096/prediction-of-n-linked-glycosylation-sites-using-position-relative-features-and-statistical-moments
#10
Muhammad Aizaz Akmal, Nouman Rasool, Yaser Daanial Khan
Glycosylation is one of the most complex post translation modification in eukaryotic cells. Almost 50% of the human proteome is glycosylated as glycosylation plays a vital role in various biological functions such as antigen's recognition, cell-cell communication, expression of genes and protein folding. It is a significant challenge to identify glycosylation sites in protein sequences as experimental methods are time taking and expensive. A reliable computational method is desirable for the identification of glycosylation sites...
2017: PloS One
https://www.readbyqxmd.com/read/28796489/rational-modular-rna-engineering-based-on-in-vivo-profiling-of-structural-accessibility
#11
Abigail N Leistra, Paul Amador, Aishwarya Buvanendiran, Alex Moon-Walker, Lydia M Contreras
Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering...
August 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28795686/hdl-and-atherosclerotic-cardiovascular-disease-genetic-insights-into-complex-biology
#12
REVIEW
Robert S Rosenson, H Bryan Brewer, Philip J Barter, Johan L M Björkegren, M John Chapman, Daniel Gaudet, Daniel Seung Kim, Eric Niesor, Kerry-Anne Rye, Frank M Sacks, Jean-Claude Tardif, Robert A Hegele
Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants...
August 10, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28794258/genetic-architecture-and-molecular-networks-underlying-leaf-thickness-in-desert-adapted-tomato
#13
Viktoriya Coneva, Margaret Frank, Maria A de Luis Balaguer, Mao Li, Rosangela Sozzani, Daniel H Chitwood
Thicker leaves allow plants to grow in water-limited conditions. However, our understanding of the genetic underpinnings of this highly functional leaf shape trait is poor. We used a custom-built confocal profilometer to directly measure leaf thickness in a set of introgression lines (ILs) derived from the desert tomato species Solanum pennellii, and identified quantitative trait loci (QTL). We report evidence of a complex genetic architecture of this trait and roles for both genetic and environmental factors...
August 9, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28778080/using-molecular-functional-networks-to-manifest-connections-between-obesity-and-obesity-related-diseases
#14
Jialiang Yang, Jing Qiu, Kejing Wang, Lijuan Zhu, Jingjing Fan, Deyin Zheng, Xiaodi Meng, Jiasheng Yang, Lihong Peng, Yu Fu, Dahan Zhang, Shouneng Peng, Haiyun Huang, Yi Zhang
Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28768814/construction-and-optimization-of-large-gene-co-expression-network-in-maize-using-rna-seq-data
#15
Ji Huang, Stefania Vendramin Alegre, Lizhen Shi, Karen McGinnis
With the emergence of massively parallel sequencing, genome-wide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a Gene Co-expression Network (GCN) can be constructed and used for gene function prediction, candidate gene selection and improving understanding of regulatory pathways. Several GCN studies have been done in maize, mostly using microarray datasets...
August 2, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28768481/piil-visualization-of-dna-methylation-and-gene-expression-data-in-gene-pathways
#16
Behrooz Torabi Moghadam, Neda Zamani, Jan Komorowski, Manfred Grabherr
BACKGROUND: DNA methylation is a major mechanism involved in the epigenetic state of a cell. It has been observed that the methylation status of certain CpG sites close to or within a gene can directly affect its expression, either by silencing or, in some cases, up-regulating transcription. However, a vertebrate genome contains millions of CpG sites, all of which are potential targets for methylation, and the specific effects of most sites have not been characterized to date. To study the complex interplay between methylation status, cellular programs, and the resulting phenotypes, we present PiiL, an interactive gene expression pathway browser, facilitating analyses through an integrated view of methylation and expression on multiple levels...
August 2, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28767659/mitochondrial-and-nuclear-dna-reveals-reticulate-evolution-in-hares-lepus-spp-lagomorpha-mammalia-from-ethiopia
#17
Zelalem Tolesa, Endashaw Bekele, Kassahun Tesfaye, Hichem Ben Slimen, Juan Valqui, Abebe Getahun, Günther B Hartl, Franz Suchentrunk
For hares (Lepus spp., Leporidae, Lagomorpha, Mammalia) from Ethiopia no conclusive molecular phylogenetic data are available. To provide a first molecular phylogenetic model for the Abyssinian Hare (Lepus habessinicus), the Ethiopian Hare (L. fagani), and the Ethiopian Highland Hare (L. starcki) and their evolutionary relationships to hares from Africa, Eurasia, and North America, we phylogenetically analysed mitochondrial ATPase subunit 6 (ATP6; n = 153 / 416bp) and nuclear transferrin (TF; n = 155 / 434bp) sequences of phenotypically determined individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28765560/machine-learning-assisted-network-inference-approach-to-identify-a-new-class-of-genes-that-coordinate-the-functionality-of-cancer-networks
#18
Mehrab Ghanat Bari, Choong Yong Ung, Cheng Zhang, Shizhen Zhu, Hu Li
Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28763475/the-bos-taurus-bos-indicus-balance-in-fertility-and-milk-related-genes
#19
Parthan Kasarapu, Laercio R Porto-Neto, Marina R S Fortes, Sigrid A Lehnert, Mauricio A Mudadu, Luiz Coutinho, Luciana Regitano, Andrew George, Antonio Reverter
Numerical approaches to high-density single nucleotide polymorphism (SNP) data are often employed independently to address individual questions. We linked independent approaches in a bioinformatics pipeline for further insight. The pipeline driven by heterozygosity and Hardy-Weinberg equilibrium (HWE) analyses was applied to characterize Bos taurus and Bos indicus ancestry. We infer a gene co-heterozygosity network that regulates bovine fertility, from data on 18,363 cattle with genotypes for 729,068 SNP. Hierarchical clustering separated populations according to Bos taurus and Bos indicus ancestry...
2017: PloS One
https://www.readbyqxmd.com/read/28753602/automated-incorporation-of-pairwise-dependency-in-transcription-factor-binding-site-prediction-using-dinucleotide-weight-tensors
#20
Saeed Omidi, Mihaela Zavolan, Mikhail Pachkov, Jeremie Breda, Severin Berger, Erik van Nimwegen
Gene regulatory networks are ultimately encoded by the sequence-specific binding of (TFs) to short DNA segments. Although it is customary to represent the binding specificity of a TF by a position-specific weight matrix (PSWM), which assumes each position within a site contributes independently to the overall binding affinity, evidence has been accumulating that there can be significant dependencies between positions. Unfortunately, methodological challenges have so far hindered the development of a practical and generally-accepted extension of the PSWM model...
July 2017: PLoS Computational Biology
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