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https://www.readbyqxmd.com/read/28226770/a-multiscale-model-based-analysis-of-the-multi-tissue-interplay-underlying-blood-glucose-regulation-in-type-i-diabetes
#1
Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Markus Krauss, Lars Kupfer, Stephan Schaller, Thomas Eissing
A multiscale model for blood glucose regulation in diabetes type I patients is constructed by integrating detailed metabolic network models for fat, liver and muscle cells into a whole body physiologically-based pharmacokinetic/pharmacodynamic (pBPK/PD) model. The blood glucose regulation PBPK/PD model simulates the distribution and metabolization of glucose, insulin and glucagon on an organ and whole body level. The genome-scale metabolic networks in contrast describe intracellular reactions. The developed multiscale model is fitted to insulin, glucagon and glucose measurements of a 48h clinical trial featuring 6 subjects and is subsequently used to simulate (in silico) the influence of geneknockouts and drug-induced enzyme inhibitions on whole body blood glucose levels...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224499/finding-rna-protein-interaction-sites-using-hmms
#2
Tao Wang, Jonghyun Yun, Yang Xie, Guanghua Xiao
RNA-binding proteins play important roles in the various stages of RNA maturation through binding to its target RNAs. Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq) has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Several Hidden Markov model-based (HMM) approaches have been suggested to identify protein-RNA binding sites from CLIP-Seq datasets. In this chapter, we describe how HMM can be applied to analyze CLIP-Seq datasets, including the bioinformatics preprocessing steps to extract count information from the sequencing data before HMM and the downstream analysis steps following peak-calling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223510/pemapper-and-pecaller-provide-a-simplified-approach-to-whole-genome-sequencing
#3
H Richard Johnston, Pankaj Chopra, Thomas S Wingo, Viren Patel, Michael P Epstein, Jennifer G Mulle, Stephen T Warren, Michael E Zwick, David J Cutler
The analysis of human whole-genome sequencing data presents significant computational challenges. The sheer size of datasets places an enormous burden on computational, disk array, and network resources. Here, we present an integrated computational package, PEMapper/PECaller, that was designed specifically to minimize the burden on networks and disk arrays, create output files that are minimal in size, and run in a highly computationally efficient way, with the single goal of enabling whole-genome sequencing at scale...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28222737/dynamic-genome-scale-metabolic-modeling-of-the-yeast-pichia-pastoris
#4
Francisco Saitua, Paulina Torres, José Ricardo Pérez-Correa, Eduardo Agosin
BACKGROUND: Pichia pastoris shows physiological advantages in producing recombinant proteins, compared to other commonly used cell factories. This yeast is mostly grown in dynamic cultivation systems, where the cell's environment is continuously changing and many variables influence process productivity. In this context, a model capable of explaining and predicting cell behavior for the rational design of bioprocesses is highly desirable. Currently, there are five genome-scale metabolic reconstructions of P...
February 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28219341/integrating-genetic-maps-in-bambara-groundnut-vigna-subterranea-l-verdc-and-their-syntenic-relationships-among-closely-related-legumes
#5
Wai Kuan Ho, Hui Hui Chai, Presidor Kendabie, Nariman Salih Ahmad, Jaeyres Jani, Festo Massawe, Andrzej Kilian, Sean Mayes
BACKGROUND: Bambara groundnut [Vigna subterranea (L) Verdc.] is an indigenous legume crop grown mainly in subsistence and small-scale agriculture in sub-Saharan Africa for its nutritious seeds and its tolerance to drought and poor soils. Given that the lack of ex ante sequence is often a bottleneck in marker-assisted crop breeding for minor and underutilised crops, we demonstrate the use of limited genetic information and resources developed within species, but linked to the well characterised common bean (Phaseolus vulgaris) genome sequence and the partially annotated closely related species; adzuki bean (Vigna angularis) and mung bean (Vigna radiata)...
February 20, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28218960/evolutionary-genetics-of-host-shifts-in-herbivorous-insects-insights-from-the-age-of-genomics
#6
Kim L Vertacnik, Catherine R Linnen
Adaptation to different host taxa is a key driver of insect diversification. Herbivorous insects are classic models for ecological and evolutionary research, but it is recent advances in sequencing, statistics, and molecular technologies that have cleared the way for investigations into the proximate genetic mechanisms underlying host shifts. In this review, we discuss how genome-scale data are revealing-at resolutions previously unimaginable-the genetic architecture of host-use traits, the causal loci underlying host shifts, and the predictability of host-use evolution...
February 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28217746/integrated-regulatory-and-metabolic-networks-of-the-marine-diatom-phaeodactylum-tricornutum-predict-the-response-to-rising-co2-levels
#7
Jennifer Levering, Christopher L Dupont, Andrew E Allen, Bernhard O Palsson, Karsten Zengler
Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean's primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom's metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels...
January 2017: MSystems
https://www.readbyqxmd.com/read/28215528/a-systematic-evaluation-of-methods-for-tailoring-genome-scale-metabolic-models
#8
Sjoerd Opdam, Anne Richelle, Benjamin Kellman, Shanzhong Li, Daniel C Zielinski, Nathan E Lewis
Genome-scale models of metabolism can illuminate the molecular basis of cell phenotypes. Since some enzymes are only active in specific cell types, several algorithms use omics data to construct cell-line- and tissue-specific metabolic models from genome-scale models. However, these methods are often not rigorously benchmarked, and it is unclear how algorithm and parameter selection (e.g., gene expression thresholds, metabolic constraints) affects model content and predictive accuracy. To investigate this, we built hundreds of models of four different cancer cell lines using six algorithms, four gene expression thresholds, and three sets of metabolic constraints...
February 14, 2017: Cell Systems
https://www.readbyqxmd.com/read/28212815/systematic-testing-of-enzyme-perturbation-sensitivities-via-graded-dcas9-modulation-in-saccharomyces-cerevisiae
#9
Matthew Deaner, Hal S Alper
Dissecting genotype-phenotype relationships in a high-throughput and scalable manner is still an unresolved problem facing metabolic engineers. While the RNA-guided nuclease Cas9 has been repurposed as a programmable transcription regulator, its application has typically been limited to binary on/off regulation and thus misses informative and potentially optimal intermediate levels of gene expression. In this work, we establish a rapid method for fine-tuned, graded expression of pathway enzymes via dCas9 regulation by varying sgRNA target location as the dominant parameter...
February 14, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28211993/recent-lab-on-chip-developments-for-novel-drug-discovery
#10
REVIEW
Nauman Khalid, Isao Kobayashi, Mitsutoshi Nakajima
Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development...
February 17, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28209199/making-life-difficult-for-clostridium-difficile-augmenting-the-pathogen-s-metabolic-model-with-transcriptomic-and-codon-usage-data-for-better-therapeutic-target-characterization
#11
Sara Saheb Kashaf, Claudio Angione, Pietro Lió
BACKGROUND: Clostridium difficile is a bacterium which can infect various animal species, including humans. Infection with this bacterium is a leading healthcare-associated illness. A better understanding of this organism and the relationship between its genotype and phenotype is essential to the search for an effective treatment. Genome-scale metabolic models contain all known biochemical reactions of a microorganism and can be used to investigate this relationship. RESULTS: We present icdf834, an updated metabolic network of C...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28195572/dna-methylation-as-a-putative-mechanism-for-reduced-dendritic-spine-density-in-the-superior-temporal-gyrus-of-subjects-with-schizophrenia
#12
B McKinney, Y Ding, D A Lewis, R A Sweet
Reduced dendritic spine density (DSD) in cortical layer 3 of the superior temporal gyrus (STG), and multiple other brain regions, is consistently observed in postmortem studies of schizophrenia (SZ). Elucidating the molecular mechanisms of this intermediate phenotype holds promise for understanding SZ pathophysiology, identifying SZ treatment targets and developing animal models. DNA methylation (DNAm), the addition of a methyl group to a cytosine nucleotide, regulates gene transcription and is a strong candidate for such a mechanism...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28191885/molecular-definition-of-a-metastatic-lung-cancer-state-reveals-a-targetable-cd109-janus-kinase-stat-axis
#13
Chen-Hua Chuang, Peyton G Greenside, Zoë N Rogers, Jennifer J Brady, Dian Yang, Rosanna K Ma, Deborah R Caswell, Shin-Heng Chiou, Aidan F Winters, Barbara M Grüner, Gokul Ramaswami, Andrew L Spencley, Kimberly E Kopecky, Leanne C Sayles, E Alejandro Sweet-Cordero, Jin Billy Li, Anshul Kundaje, Monte M Winslow
Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival...
February 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28189107/c-elegans-and-its-bacterial-diet-as-a-model-for-systems-level-understanding-of-host-microbiota-interactions
#14
REVIEW
Jingyan Zhang, Amy D Holdorf, Albertha Jm Walhout
Resident microbes of the human body, particularly the gut microbiota, provide essential functions for the host, and, therefore, have important roles in human health as well as mitigating disease. It is difficult to study the mechanisms by which the microbiota affect human health, especially at a systems-level, due to heterogeneity of human genomes, the complexity and heterogeneity of the gut microbiota, the challenge of growing these bacteria in the laboratory, and the lack of bacterial genetics in most microbiotal species...
February 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28187415/estimation-of-biomass-composition-from-genomic-and-transcriptomic-information
#15
Sophia Santos, Isabel Rocha
Given the great potential impact of the growing number of complete genome-scale metabolic network reconstructions of microorganisms, bioinformatics tools are needed to simplify and accelerate the course of knowledge in this field. One essential component of a genome-scale metabolic model is its biomass equation, whose maximization is one of the most common objective functions used in Flux Balance Analysis formulations. Some components of biomass, such as amino acids and nucleotides, can be estimated from genome information, providing reliable data without the need of performing lab experiments...
November 27, 2016: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28187207/a-multi-objective-constraint-based-approach-for-modeling-genome-scale-microbial-ecosystems
#16
Marko Budinich, Jérémie Bourdon, Abdelhalim Larhlimi, Damien Eveillard
Interplay within microbial communities impacts ecosystems on several scales, and elucidation of the consequent effects is a difficult task in ecology. In particular, the integration of genome-scale data within quantitative models of microbial ecosystems remains elusive. This study advocates the use of constraint-based modeling to build predictive models from recent high-resolution -omics datasets. Following recent studies that have demonstrated the accuracy of constraint-based models (CBMs) for simulating single-strain metabolic networks, we sought to study microbial ecosystems as a combination of single-strain metabolic networks that exchange nutrients...
2017: PloS One
https://www.readbyqxmd.com/read/28186904/a-combined-pls-and-negative-binomial-regression-model-for-inferring-association-networks-from-next-generation-sequencing-count-data
#17
Maiju Pesonen, Jaakko Nevalainen, Steven Potter, Somnath Datta, Susmita Datta
A major challenge of genomics data is to detect interactions displaying functional associations from large-scale observations. In this study, a new cPLS-algorithm combining partial least squares approach with negative binomial regression is suggested to reconstruct a genomic association network for high-dimensional next-generation sequencing count data. The suggested approach is applicable to the raw counts data, without requiring any further pre-processing steps. In the settings investigated, the cPLS-algorithm outperformed the two widely used comparative methods, graphical lasso and weighted correlation network analysis...
February 7, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28185578/fast-ancestral-gene-order-reconstruction-of-genomes-with-unequal-gene-content
#18
Pedro Feijão, Eloi Araujo
BACKGROUND: During evolution, genomes are modified by large scale structural events, such as rearrangements, deletions or insertions of large blocks of DNA. Of particular interest, in order to better understand how this type of genomic evolution happens, is the reconstruction of ancestral genomes, given a phylogenetic tree with extant genomes at its leaves. One way of solving this problem is to assume a rearrangement model, such as Double Cut and Join (DCJ), and find a set of ancestral genomes that minimizes the number of events on the input tree...
November 11, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28185400/microdiversity-shapes-the-traits-niche-space-and-biogeography-of-microbial-taxa
#19
REVIEW
Alyse A Larkin, Adam C Martiny
With rapidly improving sequencing technologies, scientists have recently gained the ability to examine diverse microbial communities at high genomic resolution, revealing that both free-living and host-associated microbes partition their environment at fine phylogenetic scales. This "microdiversity," or closely related (>97% similar 16S rRNA gene) but ecologically and physiologically distinct sub-taxonomic groups, appears to be an intrinsic property of microorganisms. However, the functional implications of microdiversity as well as its effects on microbial biogeography are poorly understood...
February 10, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28179641/shank-proteins-roles-at-the-synapse-and-in-autism-spectrum-disorder
#20
REVIEW
Patricia Monteiro, Guoping Feng
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour...
March 2017: Nature Reviews. Neuroscience
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