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Expression genomic integration

Maxime Lamontagne, Jean-Christophe Bérubé, Ma'en Obeidat, Michael H Cho, Brian D Hobbs, Phuwanat Sakornsakolpat, Kim de Jong, H Marike Boezen, David Nickle, Ke Hao, Wim Timens, Maarten van den Berge, Philippe Joubert, Michel Laviolette, Don D Sin, Peter D Paré, Yohan Bossé
Causal genes of chronic obstructive pulmonary disease (COPD) remain elusive. The current study aims at integrating genome-wide association studies (GWAS) and lung expression quantitative loci (eQTL) data to map COPD candidate causal genes and gain biological insights into the recently discovered COPD susceptibility loci. Two complementary genomic datasets on COPD were studied. First, the lung eQTL dataset which included whole-genome gene expression and genotyping data from 1,038 individuals. Second, the largest COPD GWAS to date from the International COPD Genetics Consortium (ICGC) with 13,710 cases and 38,062 controls...
March 14, 2018: Human Molecular Genetics
Christos Dimitrakopoulos, Sravanth Kumar Hindupur, Luca Häfliger, Jonas Behr, Hesam Montazeri, Michael N Hall, Niko Beerenwinkel
Motivation: Several molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions, and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression...
March 14, 2018: Bioinformatics
R Cameron Coates, Benjamin P Bowen, Ernst Oberortner, Linda Thomashow, Michalis Hadjithomas, Zhiying Zhao, Jing Ke, Leslie Silva, Katherine Louie, Gaoyan Wang, David Robinson, Angela Tarver, Matthew Hamilton, Andrea Lubbe, Meghan Feltcher, Jeffery L Dangl, Amrita Pati, David Weller, Trent R Northen, Jan-Fang Cheng, Nigel J Mouncey, Samuel Deutsch, Yasuo Yoshikuni
Increasing availability of new genomes and putative biosynthetic gene clusters (BGCs) has extended the opportunity to access novel chemical diversity for agriculture, medicine, environmental and industrial purposes. However, functional characterization of BGCs through heterologous expression is limited because expression may require complex regulatory mechanisms, specific folding or activation. We developed an integrated workflow for BGC characterization that integrates pathway identification, modular design, DNA synthesis, assembly and characterization...
March 15, 2018: Journal of Industrial Microbiology & Biotechnology
Suhong Xiao, Ying-Sheng Tang, Praveen Kusumanchi, Sally P Stabler, Ying Zhang, Asok C Antony
Background: Epidemiologic and in vitro studies suggest independent linkages between poor folate and/or vitamin B-12 nutrition, genomic human papillomavirus (HPV) type 16 viral integration, and cancer. However, there is no direct evidence in vivo to support the causative role of poor folate nutrition in HPV16 integration into the cellular genome. Objective: We tested the hypothesis that folate deficiency enables the integration of HPV16 into the genome of HPV16-harboring keratinocytes, and could thereby influence earlier transformation of these cells to cancer in an animal model...
March 1, 2018: Journal of Nutrition
Zhong Ni, Xiting Wang, Tianchen Zhang, Linlin Li, Jianxue Li
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database...
April 2018: Experimental and Therapeutic Medicine
Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Jingxiao Wang, Xinjie Yang, Haibo Han, Limin Wang, Weiqian Bao, Shanshan Wang, Robert M Hoffman, Meng Yang, Hui Qi, Chao An, Kaiwen Hu
Objective: Triple-negative breast cancer (TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu (TBM), the rhizome of Bolbostemma paniculatum (Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu (ETBM) on TNBC orthotopic mouse models and cell lines. Methods: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Changguo Ma, Chunjie Gu, Yongxia Huo, Xiaoyan Li, Xiong-Jian Luo
Genome-wide association studies (GWAS) have identified more than 100 loci that show robust association with schizophrenia risk. However, due to the complexity of linkage disequilibrium and gene regulatory, it is challenging to pinpoint the causal genes at the risk loci and translate the genetic findings from GWAS into disease mechanism and clinical treatment. Here we systematically predicted the plausible candidate causal genes for schizophrenia at genome-wide level. We utilized different approaches and strategies to predict causal genes for schizophrenia, including Sherlock, SMR, DAPPLE, Prix Fixe, NetWAS, and DEPICT...
March 15, 2018: Translational Psychiatry
Alberto J Leon, Viktoriya Borisevich, Nahal Boroumand, Robert Seymour, Rebecca Nusbaum, Olivier Escaffre, Luoling Xu, David J Kelvin, Barry Rockx
Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur...
March 14, 2018: PLoS Neglected Tropical Diseases
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as one disease, accumulated evidences point to the clinical heterogeneity of this disease which translates into disparity in outcomes between patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last ten years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 14, 2018: Annals of Medicine
Chenhui Qiu, Yuanyuan Wang, Yanen Guo, Shunren Xia
Image fusion techniques can integrate the information from different imaging modalities to get a composite image which is more suitable for human visual perception and further image processing tasks. Fusing green fluorescent protein (GFP) and phase contrast images is very important for subcellular localization, functional analysis of protein and genome expression. The fusion method of GFP and phase contrast images based on complex shearlet transform (CST) is proposed in this paper. Firstly the GFP image is converted to IHS model and its intensity component is obtained...
March 14, 2018: Microscopy Research and Technique
Xiang Zhang, Adil Mardinoglu, Leo A B Joosten, Jan A Kuivenhoven, Yang Li, Mihai G Netea, Albert K Groen
Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi , lipopolysaccharide, and Mycobacterium tuberculosis in vitro . By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation...
2018: Frontiers in Physiology
Yanhong Yang, Na Zhang, Kundong Li, Juan Chen, Lang Qiu, Jufeng Zhang
Purpose: Berberine (BBR) is a traditional Chinese medicine normally used for gastroenteritis, and recent research found that it could fight against tumors. In this study, we focused on integrating miRNA sequencing and RNA sequencing of SGC-7901 gastric cancer cells treated by BBR to elucidate their underlying mechanisms. Materials and methods: WST-1 assay and flow cytometry were used to check the effects of BBR on SGC-7901. miRNA sequencing and RNA sequencing were used to establish the miRNA and mRNA profiles of BBR-treated SGC-7901...
2018: Drug Design, Development and Therapy
Nirmesh Patel, Daniel Weekes, Konstantinos Drosopoulos, Patrycja Gazinska, Elodie Noel, Mamun Rashid, Hasan Mirza, Jelmar Quist, Fara Brasó-Maristany, Sumi Mathew, Riccardo Ferro, Ana Mendes Pereira, Cynthia Prince, Farzana Noor, Erika Francesch-Domenech, Rebecca Marlow, Emanuele de Rinaldis, Anita Grigoriadis, Spiros Linardopoulos, Pierfrancesco Marra, Andrew N J Tutt
Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies and validates gene addictions in TNBCs. CNAs and gene expression alterations are integrated and genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these genes using RNAi in breast cancer and non-malignant cells, validating malignant cell selective dependence upon 37 of 130 genes...
March 13, 2018: Nature Communications
Yara Suliman, Frank Becker, Klaus Wimmers
Poor fertility of breeding stallions is a recognised problem in the equine industry. The aim of the present study was to detect molecular pathways using two groups of stallions that differed in pregnancy rates as well as in the proportion of normal and motile spermatozoa. RNA was isolated from spermatozoa of each stallion and microarray data were analysed to obtain a list of genes for which transcript abundance differed between the groups (P ≤0.05, fold change ≥1.2). In all, there were 437 differentially expressed (DE) genes between the two groups (P ≤ 0...
March 14, 2018: Reproduction, Fertility, and Development
Peng Wu, Jia-Li Liu, Shi-Mei Pei, Chang-Peng Wu, Kai Yang, Shu-Peng Wang, Song Wu
BACKGROUND: Renal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. ccRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. To improve accuracy and personalized care and increase the cure rate of cancer, molecular typing for individuals is necessary. METHODS: We adopted the genome, transcriptome and methylation HMK450 data of ccRCC in The Cancer Genome Atlas Network in this research...
March 13, 2018: BMC Cancer
Sathvik X Palakurty, John R Stinchcombe, Michelle E Afkhami
A mechanistic understanding of community ecology requires tackling the nonadditive effects of multispecies interactions, a challenge that necessitates integration of ecological and molecular complexity- namely moving beyond pairwise ecological interaction studies and the 'gene at a time' approach to mechanism. Here, we investigate the consequences of multispecies mutualisms for the structure and function of genome-wide differential coexpression networks for the first time, using the tractable and ecologically-important interaction between legume Medicago truncatula, rhizobia, and mycorrhizal fungi...
March 13, 2018: Molecular Ecology
P K Christova, N K Christov, P V Mladenov, R Imai
Expression of the TaMDC1 in transgenic tomato plants confer resistance to bacterial and fungal pathogens, as well as an insect pest and thus prove in planta function of the wheat cystatin. Cystatins are the polypeptides with cysteine proteinase inhibitory activities. Plant cystatins or phytocystatins are known to contribute to plant resistance against insect pests. Recently, increasing data proved that some of the phytocystatins also have antifungal activities in vitro. Here, we functionally characterized a wheat multidomain cystatin, TaMDC1, using in planta assays...
March 12, 2018: Plant Cell Reports
Alex Bronstein, Shay Bramson, Keren Shemesh, Batia Liefshitz, Martin Kupiec
Proper DNA damage repair is one of the most vital and fundamental functions of every cell. Several different repair mechanisms exist to deal with various types of DNA damage, in various stages of the cell cycle and under different conditions. Homologous recombination is one of the most important repair mechanisms in all organisms. Srs2, a regulator of homologous recombination, is a DNA helicase involved in DNA repair, cell cycle progression and genome integrity. Srs2 can remove Rad51 from ssDNA, and is thought to inhibit unscheduled recombination...
March 12, 2018: G3: Genes—Genomes—Genetics
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