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Combinatorial genomics

Runhua Lei, Cynthia L Frasier, Melissa T R Hawkins, Shannon E Engberg, Carolyn A Bailey, Steig E Johnson, Adam T McLain, Colin P Groves, George H Perry, Stephen D Nash, Russell A Mittermeier, Edward E Louis
The family Lepilemuridae includes 26 species of sportive lemurs, most of which were recently described. The cryptic morphological differences confounded taxonomy until recent molecular studies; however, some species' boundaries remain uncertain. To better understand the genus Lepilemur, we analyzed 35 complete mitochondrial genomes representing all recognized 26 sportive lemur taxa and estimated divergence dates. With our dataset we recovered 25 reciprocally monophyletic lineages, as well as an admixed clade containing Lepilemur mittermeieri and Lepilemur dorsalis Using modern distribution data, an ancestral area reconstruction and an ecological vicariance analysis were performed to trace the history of diversification and to test biogeographic hypotheses...
October 3, 2016: Journal of Heredity
Juan Xu, ZiShan Wang, Shengli Li, Juan Chen, Jinwen Zhang, Chunjie Jiang, Zheng Zhao, Jing Li, Yongsheng Li, Xia Li
Although systematic genomic studies have identified a broad spectrum of non-coding RNAs (ncRNAs) that are involved in breast cancer, our understanding of the epigenetic dysregulation of those ncRNAs remains limited. Here, we systematically analysed the epigenetic alterations of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in two breast cancer subtypes (luminal and basal). Widespread epigenetic alterations of miRNAs and lncRNAs were observed in both cancer subtypes. In contrast to protein-coding genes, the majority of epigenetically dysregulated ncRNAs were shared between subtypes, but a subset of transcriptomic and corresponding epigenetic changes occurred in a subtype-specific manner...
October 14, 2016: Briefings in Bioinformatics
Alan S L Wong, Gigi C G Choi, Timothy K Lu
High-order interactions among components of interconnected genetic networks regulate complex functions in biological systems, but deciphering these interactions is challenging. New strategies are emerging to decode these combinatorial genetic interactions across a wide range of organisms. Here, we review advances in multiplexed and combinatorial genetic perturbation technologies and high-throughput profiling platforms that are enabling the systematic dissection of complex genetic networks. These rapidly evolving technologies are being harnessed to probe combinatorial gene functions in functional genomics studies and have the potential to advance our understanding of how genetic networks regulate sophisticated biological phenotypes, to generate novel therapeutic strategies, and to enable the engineering of complex artificial gene networks...
October 6, 2016: Annual Review of Genetics
Tzu-Fang Lou, Chase A Weidmann, Jordan Killingsworth, Traci M Tanaka Hall, Aaron C Goldstrohm, Zachary T Campbell
RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way...
October 8, 2016: Methods: a Companion to Methods in Enzymology
Barry M Zee, Amy B Dibona, Artyom A Alekseyenko, Christopher A French, Mitzi I Kuroda
Defects in chromatin proteins frequently manifest in diseases. A striking case of a chromatin-centric disease is NUT-midline carcinoma (NMC), which is characterized by expression of NUT as a fusion partner most frequently with BRD4. ChIP-sequencing studies from NMC patients revealed that BRD4-NUT (B4N) covers large genomic regions and elevates transcription within these domains. To investigate how B4N modulates chromatin, we performed affinity purification of B4N when ectopically expressed in 293-TREx cells and quantified the associated histone posttranslational modifications (PTM) using proteomics...
2016: PloS One
Xiujuan Zhang, Ying Chen, Ying Ye, Jianfeng Wang, Hong Wang, Guohong Yuan, Zhe Lin, Yihui Wu, Yan Zhang, Xinhua Lin
Wnt signaling plays essential roles in both embryonic pattern formation and postembryonic tissue homoestasis. High levels of Wnt activity repress foregut identity and facilitate hindgut fate through forming a gradient of Wnt signaling activity along the anterior-posterior axis. Here, we examined the mechanisms of Wnt signaling in hindgut development by differentiating human embryonic stem cells (hESCs) into the hindgut progenitors. We observed severe morphological changes when Wnt signaling was blocked by using Wnt antagonist Dkk1...
September 29, 2016: Cellular Signalling
Enrique Caso, Antonio Maestro, Cristina C Sabiers, Manuel Godino, Zaira Caracuel, Joana Pons, F Jesus Gonzalez, Rocio Bautista, M Gonzalo Claros, Jaime Caso-Onzain, Elena Viejo-Allende, Peter V Giannoudis, Sara Alvarez, Paolo Maietta, Enrique Guerado
Familial predisposition is among the major genetic risk factors for non-contact musculoskeletal tissue injuries. Personal genome sequence shows that different polymorphism profiles may account for the number and the degree of injuries and the recovery time. Genotyping studies allow investigation into genome factors with potential impact on pathogenesis of non-contact ligament injuries. We have studied a family with twin sibling males surgically diagnosed of an anterior cruciate ligament non-contact rupture and non-affected progenitors (father and mother) were subjected to whole exome sequencing (WES) analysis...
September 2016: Injury
Daniel R Zerbino, Tracy Ballinger, Benedict Paten, Glenn Hickey, David Haussler
BACKGROUND: The study of genomic variation has provided key insights into the functional role of mutations. Predominantly, studies have focused on single nucleotide variants (SNV), which are relatively easy to detect and can be described with rich mathematical models. However, it has been observed that genomes are highly plastic, and that whole regions can be moved, removed or duplicated in bulk. These structural variants (SV) have been shown to have significant impact on phenotype, but their study has been held back by the combinatorial complexity of the underlying models...
September 29, 2016: BMC Bioinformatics
Afreenish Hassan, Anam Naz, Ayesha Obaid, Rehan Zafar Paracha, Kanwal Naz, Faryal Mehwish Awan, Syed Aun Muhmmad, Hussnain Ahmed Janjua, Jamil Ahmad, Amjad Ali
BACKGROUND: Acinetobacter baumannii has emerged as a significant nosocomial pathogen during the last few years, exhibiting resistance to almost all major classes of antibiotics. Alternative treatment options such as vaccines tend to be most promising and cost effective approaches against this resistant pathogen. In the current study, we have explored the pan-genome of A. baumannii followed by immune-proteomics and reverse vaccinology approaches to identify potential core vaccine targets...
2016: BMC Genomics
Nelson H Davila Olivas, Willem Kruijer, Gerrit Gort, Cris L Wijnen, Joop J A van Loon, Marcel Dicke
Plants are commonly exposed to abiotic and biotic stresses. We used 350 Arabidopsis thaliana accessions grown under controlled conditions. We employed genome-wide association analysis to investigate the genetic architecture and underlying loci involved in genetic variation in resistance to: two specialist insect herbivores, Pieris rapae and Plutella xylostella; and combinations of stresses, i.e. drought followed by P. rapae and infection by the fungal pathogen Botrytis cinerea followed by infestation by P...
September 8, 2016: New Phytologist
J Demongeot, H Hazgui
The French school of theoretical biology has been mainly initiated in Poitiers during the sixties by scientists like J. Besson, G. Bouligand, P. Gavaudan, M. P. Schützenberger and R. Thom, launching many new research domains on the fractal dimension, the combinatorial properties of the genetic code and related amino-acids as well as on the genetic regulation of the biological processes. Presently, the biological science knows that RNA molecules are often involved in the regulation of complex genetic networks as effectors, e...
September 3, 2016: Acta Biotheoretica
Barbara Mandriani, Stefano Castellana, Carmela Rinaldi, Marta Manzoni, Santina Venuto, Eva Rodriguez-Aznar, Juan Galceran, M Angela Nieto, Giuseppe Borsani, Eugenio Monti, Tommaso Mazza, Giuseppe Merla, Lucia Micale
To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species...
2016: Scientific Reports
Panagiotis Moulos, Martina Samiotaki, George Panayotou, Skarlatos G Dedos
The cells of prothoracic glands (PG) are the main site of synthesis and secretion of ecdysteroids, the biochemical products of cholesterol conversion to steroids that shape the morphogenic development of insects. Despite the availability of genome sequences from several insect species and the extensive knowledge of certain signalling pathways that underpin ecdysteroidogenesis, the spectrum of signalling molecules and ecdysteroidogenic cascades is still not fully comprehensive. To fill this gap and obtain the complete list of cell membrane receptors expressed in PG cells, we used combinatory bioinformatic, proteomic and transcriptomic analysis and quantitative PCR to annotate and determine the expression profiles of genes identified as putative cell membrane receptors of the model insect species, Bombyx mori, and subsequently enrich the repertoire of signalling pathways that are present in its PG cells...
2016: Scientific Data
Leonie Greipel, Sebastian Fischer, Jens Klockgether, Marie Dorda, Samira Mielke, Lutz Wiehlmann, Nina Cramer, Burkhard Tümmler
The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic...
August 29, 2016: Antimicrobial Agents and Chemotherapy
Mohammad Tauqeer Alam, Aleksej Zelezniak, Michael Mülleder, Pavel Shliaha, Roland Schwarz, Floriana Capuano, Jakob Vowinckel, Elahe Radmaneshfar, Antje Krüger, Enrica Calvani, Steve Michel, Stefan Börno, Stefan Christen, Kiran Raosaheb Patil, Bernd Timmermann, Kathryn S Lilley, Markus Ralser
The regulation of gene expression in response to nutrient availability is fundamental to the genotype-phenotype relationship. The metabolic-genetic make-up of the cell, as reflected in auxotrophy, is hence likely to be a determinant of gene expression. Here, we address the importance of the metabolic-genetic background by monitoring transcriptome, proteome and metabolome in a repertoire of 16 Saccharomyces cerevisiae laboratory backgrounds, combinatorially perturbed in histidine, leucine, methionine and uracil biosynthesis...
2016: Nature Microbiology
Min Zhao, Zhongming Zhao
BACKGROUND: Tumor suppressor genes (TSGs) encode the guardian molecules to control cell growth. The genomic alteration of TSGs may cause tumorigenesis and promote cancer progression. So far, investigators have mainly studied the functional effects of somatic single nucleotide variants in TSGs. Copy number variation (CNV) is another important form of genetic variation, and is often involved in cancer biology and drug treatment, but studies of CNV in TSGs are less represented in literature...
2016: BMC Genomics
Jack P Hou, Amin Emad, Gregory J Puleo, Jian Ma, Olgica Milenkovic
MOTIVATION: Cancer genomes exhibit a large number of different alterations that affect many genes in a diverse manner. An improved understanding of the generative mechanisms behind the mutation rules and their influence on gene community behavior is of great importance for the study of cancer. RESULTS: To expand our capability to analyze combinatorial patterns of cancer alterations, we developed a rigorous methodology for cancer mutation pattern discovery based on a new, constrained form of correlation clustering...
August 18, 2016: Bioinformatics
Michael W M Kühn, Evelyn Song, Zhaohui Feng, Amit Sinha, Chun-Wei Chen, Aniruddha J Deshpande, Monica Cusan, Noushin Farnoud, Annalisa Mupo, Carolyn Grove, Richard Koche, James E Bradner, Elisa de Stanchina, George S Vassiliou, Takayuki Hoshii, Scott A Armstrong
: Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known about how mutant NPM1 (NPM1(mut)) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1(mut) AML...
October 2016: Cancer Discovery
Sarah Kinkley, Johannes Helmuth, Julia K Polansky, Ilona Dunkel, Gilles Gasparoni, Sebastian Fröhler, Wei Chen, Jörn Walter, Alf Hamann, Ho-Ryun Chung
The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells...
2016: Nature Communications
Ann-Kathrin Löbs, Jyun-Liang Lin, Megan Cook, Ian Wheeldon
Advances in genome and metabolic pathway engineering have enabled large combinatorial libraries of mutant microbial hosts for chemical biosynthesis. Despite these advances, strain development is often limited by the lack of high throughput functional assays for effective library screening. Recent synthetic biology efforts have engineered microbes that synthesize acetyl and acyl esters and many yeasts naturally produce esters to significant titers. Short and medium chain volatile esters have value as fragrance and flavor compounds, while long chain acyl esters are potential replacements for diesel fuel...
October 2016: Biotechnology Journal
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