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https://www.readbyqxmd.com/read/28527885/maintenance-of-atp-homeostasis-triggers-metabolic-shifts-in-gas-fermenting-acetogens
#1
Kaspar Valgepea, Renato de Souza Pinto Lemgruber, Kieran Meaghan, Robin William Palfreyman, Tanus Abdalla, Björn Daniel Heijstra, James Bruce Behrendorff, Ryan Tappel, Michael Köpke, Séan Dennis Simpson, Lars Keld Nielsen, Esteban Marcellin
Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1...
May 16, 2017: Cell Systems
https://www.readbyqxmd.com/read/28525968/survivalgwas_sv-software-for-the-analysis-of-genome-wide-association-studies-of-imputed-genotypes-with-time-to-event-outcomes
#2
Hamzah Syed, Andrea L Jorgensen, Andrew P Morris
BACKGROUND: Analysis of genome-wide association studies (GWAS) with "time to event" outcomes have become increasingly popular, predominantly in the context of pharmacogenetics, where the survival endpoint could be death, disease remission or the occurrence of an adverse drug reaction. However, methodology and software that can efficiently handle the scale and complexity of genetic data from GWAS with time to event outcomes has not been extensively developed. RESULTS: SurvivalGWAS_SV is an easy to use software implemented using C# and run on Linux, Mac OS X & Windows operating systems...
May 19, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28521784/functional-regression-method-for-whole-genome-eqtl-epistasis-analysis-with-sequencing-data
#3
Kelin Xu, Li Jin, Momiao Xiong
BACKGROUND: Epistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves...
May 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28520105/large-scale-computational-models-of-liver-metabolism-how-far-from-the-clinics
#4
REVIEW
Tanja Cvitanović, Matthias C Reichert, Miha Moškon, Miha Mraz, Frank Lammert, Damjana Rozman
Understanding the dynamics of human liver metabolism is fundamental for effective diagnosis and treatment of liver diseases in general and the metabolism of drugs in particular. This knowledge can be obtained with systems biology/medicine approaches that account for the complexity of hepatic responses and their systemic consequences in other organs. Computational modelling can reveal hidden principles of the system by classification of individual components, analysing their interactions and simulating the effects that are difficult to investigate experimentally...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28516784/in-culture-cross-linking-of-bacterial-cells-reveals-large-scale-dynamic-protein-protein-interactions-at-the-peptide-level
#5
Luitzen de Jong, Edward A de Koning, Winfried Roseboom, Hansuk Buncherd, Martin J Wanner, Irena Dapic, Petra J Jansen, Jan H van Maarseveen, Garry L Corthals, Peter J Lewis, Leendert Willem Hamoen, Chris G de Koster
Identification of dynamic protein-protein interactions at the peptide level on a proteomic scale is a challenging approach that is still in its infancy. We have developed a system to cross-link cells directly in culture with the special lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the Gram positive model bacterium Bacillus subtilis as an exemplar system. Within 5 min extensive intracellular cross-linking was detected, while intracellular cross-linking in a Gram-negative species, Escherichia coli, was still undetectable after 30 min, in agreement with the low permeability in this organism for lipophilic compounds like BAMG...
May 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28515774/complexity-and-algorithms-for-copy-number-evolution-problems
#6
Mohammed El-Kebir, Benjamin J Raphael, Ron Shamir, Roded Sharan, Simone Zaccaria, Meirav Zehavi, Ron Zeira
BACKGROUND: Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along a chromosome constitutes the chromosome's copy-number profile. Understanding how such profiles evolve in cancer can assist in both diagnosis and prognosis. RESULTS: We model the evolution of a tumor by segmental deletions and amplifications, and gauge distance from profile [Formula: see text] to [Formula: see text] by the minimum number of events needed to transform [Formula: see text] into [Formula: see text]...
2017: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/28511701/easi-crispr-a-robust-method-for-one-step-generation-of-mice-carrying-conditional-and-insertion-alleles-using-long-ssdna-donors-and-crispr-ribonucleoproteins
#7
Rolen M Quadros, Hiromi Miura, Donald W Harms, Hisako Akatsuka, Takehito Sato, Tomomi Aida, Ronald Redder, Guy P Richardson, Yutaka Inagaki, Daisuke Sakai, Shannon M Buckley, Parthasarathy Seshacharyulu, Surinder K Batra, Mark A Behlke, Sarah A Zeiner, Ashley M Jacobi, Yayoi Izu, Wallace B Thoreson, Lisa D Urness, Suzanne L Mansour, Masato Ohtsuka, Channabasavaiah B Gurumurthy
BACKGROUND: Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models...
May 17, 2017: Genome Biology
https://www.readbyqxmd.com/read/28511646/emergence-of-microbial-diversity-due-to-cross-feeding-interactions-in-a-spatial-model-of-gut-microbial-metabolism
#8
Milan J A van Hoek, Roeland M H Merks
BACKGROUND: The human gut contains approximately 10(14) bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28510587/sibling-method-increases-risk-assessment-estimates-for-type-1-diabetes
#9
Hoang V Lam, Dat T Nguyen, Cao D Nguyen
We presented a risk assessment model to distinguish between type 1 diabetes (T1D) affected and unaffected siblings using only three single nucleotide polymorphism (SNP) genotypes. In addition we calculated the heritability from genome-wide identity-by-descent (IBD) sharing between full siblings. We analyzed 1,253 pairs of affected individuals and their unaffected siblings (750 pairs from a discovery set and 503 pairs from a validation set) from the T1D Genetics Consortium (T1DGC), applying a logistic regression to analyze the area under the receiver operator characteristic (ROC) curve (AUC)...
2017: PloS One
https://www.readbyqxmd.com/read/28509388/proteomic-explorations-of-autism-spectrum-disorder
#10
Nicholas Szoko, Adam J McShane, Marvin R Natowicz
Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue...
May 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/28505334/direction-a-machine-learning-framework-for-predicting-and-characterizing-dna-methylation-and-hydroxymethylation-in-mammalian-genomes
#11
Milos Pavlovic, Pradipta Ray, Kristina Pavlovic, Aaron Kotamarti, Min Chen, Michael Q Zhang
Motivation: 5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major epigenetic modifications known to significantly alter mammalian gene expression. High-throughput assays to detect these modifications are expensive, labor-intensive, unfeasible in some contexts, and leave a portion of the genome unqueried. Hence, we devised a novel, supervised, integrative learning framework to perform whole-genome methylation and hydroxymethylation predictions in CpG dinucleotides. Our framework can also perform imputation of missing or low quality data in existing sequencing datasets...
May 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28505184/steadycom-predicting-microbial-abundances-while-ensuring-community-stability
#12
Siu Hung Joshua Chan, Margaret N Simons, Costas D Maranas
Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism. Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems. While several modeling techniques have been developed for microbial communities, little emphasis has been placed on the need to impose a time-averaged constant growth rate across all members for a community to ensure co-existence and stability...
May 15, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28503451/association-between-a-polymorphism-in-casp3-and-casp9-genes-and-ischemic-stroke
#13
Bae Youl Lee, Jinmann Chon, Hee-Sang Kim, Jong Ha Lee, Dong Hwan Yun, Seung Don Yoo, Dong Hwan Kim, Seung Ah Lee, Yoo Jin Han, Hyunseok Lee, Jin Chul Kim, Yunsoo Soh, Joo-Ho Chung, Su Kang Kim, Hae Jeong Park
OBJECTIVE: To investigate whether the polymorphisms of CASP3 gene (rs4647602, intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and rs1052571, Ser/Val T/C) were associated with the development, and clinical severity of ischemic stroke and functional consequences after stroke. METHODS: Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects were extracted, and polymerase chain reaction products were sequenced. To investigate the association of polymorphisms and the development, and National Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were analyzed...
April 2017: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/28498906/heap-a-highly-sensitive-and-accurate-snp-detection-tool-for-low-coverage-high-throughput-sequencing-data
#14
Masaaki Kobayashi, Hajime Ohyanagi, Hideki Takanashi, Satomi Asano, Toru Kudo, Hiromi Kajiya-Kanegae, Atsushi J Nagano, Hitoshi Tainaka, Tsuyoshi Tokunaga, Takashi Sazuka, Hiroyoshi Iwata, Nobuhiro Tsutsumi, Kentaro Yano
Recent availability of large-scale genomic resources enables us to conduct so called genome-wide association studies (GWAS) and genomic prediction (GP) studies, particularly with next-generation sequencing (NGS) data. The effectiveness of GWAS and GP depends on not only their mathematical models, but the quality and quantity of variants employed in the analysis. In NGS single nucleotide polymorphism (SNP) calling, conventional tools ideally require more reads for higher SNP sensitivity and accuracy. In this study, we aimed to develop a tool, Heap, that enables robustly sensitive and accurate calling of SNPs, particularly with a low coverage NGS data, which must be aligned to the reference genome sequences in advance...
May 11, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28495970/high-throughput-biochemical-profiling-reveals-sequence-determinants-of-dcas9-off-target-binding-and-unbinding
#15
Evan A Boyle, Johan O L Andreasson, Lauren M Chircus, Samuel H Sternberg, Michelle J Wu, Chantal K Guegler, Jennifer A Doudna, William J Greenleaf
The bacterial adaptive immune system CRISPR-Cas9 has been appropriated as a versatile tool for editing genomes, controlling gene expression, and visualizing genetic loci. To analyze Cas9's ability to bind DNA rapidly and specifically, we generated multiple libraries of potential binding partners for measuring the kinetics of nuclease-dead Cas9 (dCas9) interactions. Using a massively parallel method to quantify protein-DNA interactions on a high-throughput sequencing flow cell, we comprehensively assess the effects of combinatorial mismatches between guide RNA (gRNA) and target nucleotides, both in the seed and in more distal nucleotides, plus disruption of the protospacer adjacent motif (PAM)...
May 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28495491/a-computational-algorithm-for-personalized-medicine-in-schizophrenia
#16
Beom S Lee, Roger S McIntyre, James E Gentle, Nan Sook Park, David A Chiriboga, Yena Lee, Sabrina Singh, Marie A McPherson
Despite advances in sequencing candidate genes and whole genomes, no method has accurately predicted who will or will not benefit from a specific antipsychotic medication among patients with schizophrenia. We propose a computational algorithm that utilizes a person-centered approach that directly identifies individual patients who will respond to a specific antipsychotic medication. The algorithm was applied to the data obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study...
May 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28486694/differential-microrna-expression-in-cultured-palatal-fibroblasts-from-infants-with-cleft-palate-and-controls
#17
Christian Schoen, Jeffrey C Glennon, Shaghayegh Abghari, Marjon Bloemen, Armaz Aschrafi, Carine E L Carels, Johannes W Von den Hoff
Background: The role of microRNAs (miRNAs) in animal models of palatogenesis has been shown, but only limited research has been carried out in humans. To date, no miRNA expression study on tissues or cells from cleft palate patients has been published. We compared miRNA expression in palatal fibroblasts from cleft palate patients and age-matched controls. Material and Methods: Cultured palatal fibroblasts from 10 non-syndromic cleft lip and palate patients (nsCLP; mean age: 18 ± 2 months), 5 non-syndromic cleft palate only patients (nsCPO; mean age: 17 ± 2 months), and 10 controls (mean age: 24 ± 5 months) were analysed with next-generation small RNA sequencing...
May 9, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28480146/development-and-application-of-14-microsatellite-markers-in-the-burying-beetle-nicrophorus-vespilloides-reveals-population-genetic-differentiation-at-local-spatial-scales
#18
Sonia Pascoal, Rebecca M Kilner
Burying beetles (genus Nicrophorus) are relatively rare among insects in providing sophisticated parental care. Consequently, they have become model species in research analysing social evolution, the evolution of parental care and mating systems. We used the recently published N. vespilloides genome and transcriptome to develop microsatellite markers. Specifically, we developed 14 polymorphic markers with five to 13 alleles per locus and used them to investigate levels of genetic differentiation in four south Cambridgeshire (UK) populations of N...
2017: PeerJ
https://www.readbyqxmd.com/read/28477434/genomic-analysis-of-a-cardinalfish-with-larval-homing-potential-reveals-genetic-admixture-in-the-okinawa-islands
#19
A L Gould, P V Dunlap
Discrepancies between potential and observed dispersal distances of reef fish indicate the need for a better understanding of the influence of larval behavior on recruitment and dispersal. Population genetic studies can reveal the degree to which populations are connected, providing insight on these patterns, and the development of restriction site associated sequencing (RAD-Seq) methods has made the study of non-model organisms more accessible. We applied double digest RAD-Seq methods to test for population differentiation in the coral reef-dwelling cardinalfish, Siphamia tubifer, which based on behavioral studies, have the potential to use navigational cues to return to natal reefs...
May 6, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28475710/an-efficient-graph-kernel-method-for-non-coding-rna-functional-prediction
#20
Nicolò Navarin, Fabrizio Costa
Motivation: The importance of RNA protein-coding gene regulation is by now well appreciated. Noncoding RNAs (ncRNAs) are known to regulate gene expression at practically every stage, ranging from chromatin packaging to mRNA translation. However the functional characterization of specific instances remains a challenging task in genome scale settings. For this reason, automatic annotation approaches are of interest. Existing computational methods are either efficient but non accurate or they offer increased precision, but present scalability problems...
May 5, 2017: Bioinformatics
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