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Network function prediction

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
Yimin Wang, Fang Ye, Chanyan Huang, Faling Xue, Yingyuan Li, Shaowei Gao, Zeting Qiu, Si Li, Qinchang Chen, Huaqiang Zhou, Yiyan Song, Wenqi Huang, Wulin Tan, Zhongxing Wang
BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected...
March 15, 2018: Clinical Journal of Pain
Caleb J Bashor, James J Collins
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function...
March 16, 2018: Annual Review of Biophysics
Marinho A Lopes, Mark P Richardson, Eugenio Abela, Christian Rummel, Kaspar Schindler, Marc Goodfellow, John R Terry
Recent studies have shown that mathematical models can be used to analyze brain networks by quantifying how likely they are to generate seizures. In particular, we have introduced the quantity termed brain network ictogenicity (BNI), which was demonstrated to have the capability of differentiating between functional connectivity (FC) of healthy individuals and those with epilepsy. Furthermore, BNI has also been used to quantify and predict the outcome of epilepsy surgery based on FC extracted from pre-operative ictal intracranial electroencephalography (iEEG)...
2018: Frontiers in Neurology
Soumya Luthra, Uma Chandran, Brenda Diergaarde, Michael Becich, Adrian V Lee, Carola A Neumann
Increased reactive species (RS; reactive oxygen and nitrogen species) are a byproduct of both enzymatic and non-enzymatic systems, and critical in cancer development, including breast tumorigenesis. To investigate the role of RS-related genes in breast cancer, expression levels of the most common annotated genes involved in regulating cellular RS levels and proteins that are substrates of RS in specific subtypes of breast cancer 9 were evaluated using public data bases. Based on the premise that increased RS promote tumor formation, and breast cancer subtypes vary in aggressiveness, we hypothesized that specific RS gene expression signatures are associated with breast cancer aggressiveness and patient survival...
March 12, 2018: Free Radical Biology & Medicine
Eli Gibson, Wenqi Li, Carole Sudre, Lucas Fidon, Dzhoshkun I Shakir, Guotai Wang, Zach Eaton-Rosen, Robert Gray, Tom Doel, Yipeng Hu, Tom Whyntie, Parashkev Nachev, Marc Modat, Dean C Barratt, Sébastien Ourselin, M Jorge Cardoso, Tom Vercauteren
BACKGROUND AND OBJECTIVES: Medical image analysis and computer-assisted intervention problems are increasingly being addressed with deep-learning-based solutions. Established deep-learning platforms are flexible but do not provide specific functionality for medical image analysis and adapting them for this domain of application requires substantial implementation effort. Consequently, there has been substantial duplication of effort and incompatible infrastructure developed across many research groups...
May 2018: Computer Methods and Programs in Biomedicine
Alessandra Livigni, Laura O'Hara, Marta E Polak, Tim Angus, Derek W Wright, Lee B Smith, Tom C Freeman
A major endeavor of systems biology is the construction of graphical and computational models of biological pathways as a means to better understand their structure and function. Here, we present a protocol for a biologist-friendly graphical modeling scheme that facilitates the construction of detailed network diagrams, summarizing the components of a biological pathway (such as proteins and biochemicals) and illustrating how they interact. These diagrams can then be used to simulate activity flow through a pathway, thereby modeling its dynamic behavior...
April 2018: Nature Protocols
Alana Grech, Emmanuel Hanert, Len McKenzie, Michael Rasheed, Christopher Thomas, Samantha Tol, Mingzhu Wang, Michelle Waycott, Jolan Wolter, Rob Coles
The rate of exchange, or connectivity, among populations effects their ability to recover after disturbance events. However, there is limited information on the extent to which populations are connected or how multiple disturbances affect connectivity, especially in coastal and marine ecosystems. We used network analysis and the outputs of a biophysical model to measure potential functional connectivity and predict the impact of multiple disturbances on seagrasses in the central Great Barrier Reef World Heritage Area (GBRWHA), Australia...
March 15, 2018: Global Change Biology
Margarita Villar, Lourdes Mateos-Hernandez, Jose de la Fuente
BACKGROUND: Why an autoimmune disease that is the main cause of the acute neuromuscular paralysis worldwide has not yet a well-characterized cause or an effective treatment? The existence of different clinical variants for the Guillain-Barré syndrome (GBS) coupled with the fact that a high number of pathogens can cause an infection that sometimes, but not always, precedes the development of the syndrome, confers a high degree of uncertainty for both prognosis and treatment. In the post-genomic era, the development of omics technologies for the high-throughput analysis of biological molecules is allowing the characterization of biological systems in a degree of depth unimaginable before...
March 14, 2018: Current Medicinal Chemistry
Dorothea L Floris, Meng-Chuan Lai, Tanmay Nath, Michael P Milham, Adriana Di Martino
Background: The male predominance in the prevalence of autism spectrum disorder (ASD) has motivated research on sex differentiation in ASD. Multiple sources of evidence have suggested a neurophenotypic convergence of ASD-related characteristics and typical sex differences. Two existing, albeit competing, models provide predictions on such neurophenotypic convergence. These two models are testable with neuroimaging. Specifically, the Extreme Male Brain (EMB) model predicts that ASD is associated with enhanced brain maleness in both males and females with ASD (i...
2018: Molecular Autism
François Ancien, Fabrizio Pucci, Maxime Godfroid, Marianne Rooman
The classification of human genetic variants into deleterious and neutral is a challenging issue, whose complexity is rooted in the large variety of biophysical mechanisms that can be responsible for disease conditions. For non-synonymous mutations in structured proteins, one of these is the protein stability change, which can lead to loss of protein structure or function. We developed a stability-driven knowledge-based classifier that uses protein structure, artificial neural networks and solvent accessibility-dependent combinations of statistical potentials to predict whether destabilizing or stabilizing mutations are disease-causing...
March 14, 2018: Scientific Reports
Matthew Tien, Aretha Fiebig, Sean Crosson
Cells adapt to shifts in their environment by remodeling transcription. Measuring changes in transcription at the genome scale is now routine, but defining the functional significance of individual genes within large gene expression datasets remains a major challenge. We applied a network-based algorithm to interrogate publicly available gene expression data to predict genes that serve major functional roles in Caulobacter crescentus stress survival. This approach identified GsrN, a conserved small RNA that is directly activated by the general stress sigma factor, σT , and functions as a potent post-transcriptional regulator of survival across distinct conditions including osmotic and oxidative stress...
March 14, 2018: ELife
M Sehmbi, C D Rowley, L Minuzzi, F Kapczinski, M Steiner, R B Sassi, N A Bock, B N Frey
OBJECTIVE: Although cognitive dysfunction persists through affective and euthymic states in bipolar disorder (BD), its neurobiological correlates remain undetermined. We explore whole-cortex intracortical myelin (ICM) and cognition in BD-I and controls. METHODS: T1 -weighted images (3T) optimized for ICM measurement were analyzed using a surface-based approach. MRI signal was sampled at cortical mid-depth. Cognitive performance was measured via standardized computerized battery and paper-and-pencil Trails B...
March 13, 2018: Acta Psychiatrica Scandinavica
Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
Chengxin Zhang, Wei Zheng, Peter L Freddolino, Yang Zhang
Homology-based transferal remains the major approach to computational protein function annotations, but it becomes increasingly unreliable when the sequence identity between query and template decreases below 30%. We propose a novel pipeline, MetaGO, to deduce Gene Ontology attributes of proteins by combining sequence homology-based annotation with low-resolution structure prediction and comparison, and partner's-homology based protein-protein network mapping. The pipeline was tested on a large-scale set of 1000 non-redundant proteins from the CAFA3 experiment...
March 10, 2018: Journal of Molecular Biology
Hailing Yang, Xiaofei Zhang, Guangda Xin
BACKGROUND: Recent studies have reported that mesenchymal stem cells (MSCs) exert therapeutic effects on the treatment of diabetic nephropathy (DN), but the underlying mechanisms remain unclear. METHODS: A dataset GSE65561 was obtained from Gene Expression Omnibus (GEO) database, which contained four healthy control samples (group 1), four healthy controls samples co-cultured with MSCs (group 2), five DN samples (group 3) and five DN samples co-cultured with MSCs (group 4)...
March 13, 2018: Renal Failure
Heng Yao, Xiaoxuan Wang, Pengcheng Chen, Ling Hai, Kang Jin, Lixia Yao, Chuanzao Mao, Xin Chen
An advanced functional understanding of omics data is important for elucidating the design logic of physiological processes in plants and effectively controlling desired traits in plants. We present the latest version of the predicted Arabidopsis interactome resource (PAIR) and of the gene set linkage analysis (GSLA) tool, which enable the interpretation of an observed transcriptomic change (differentially expressed genes, DEGs) in Arabidopsis with respect to its functional impact for biological processes. PAIR v5...
March 12, 2018: Plant Physiology
Jonathan P Rehfuss, Kenneth M DeSart, Jared M Rozowsky, Kerri A O'Malley, Lyle L Moldawer, Henry V Baker, Yaqun Wang, Rongling Wu, Peter R Nelson, Scott A Berceli
BACKGROUND: Despite being the definitive treatment for lower extremity peripheral arterial disease, vein bypass grafts fail in half of all cases. Early repair mechanisms after implantation, governed largely by the immune environment, contribute significantly to long-term outcomes. The current study investigates the early response patterns of circulating monocytes as a determinant of graft outcome. METHODS: In 48 patients undergoing infrainguinal vein bypass grafting, the transcriptomes of circulating monocytes were analyzed preoperatively and at 1, 7, and 28 days post-operation...
March 2018: Circ Genom Precis Med
John R Fedota, Xiaoyu Ding, Allison L Matous, Betty Jo Salmeron, Michael R McKenna, Hong Gu, Thomas J Ross, Elliot A Stein
BACKGROUND: Insular subdivisions show distinct patterns of resting-state functional connectivity (rsFC) with specific brain regions, each with different functional significance. Seeds in these subdivisions are employed to characterize the effects of acute nicotine abstinence on rsFC between insula subdivisions and brain networks implicated in addiction and attentional control. METHODS: In a within-subjects design, resting-state blood oxygen level-dependent data were collected from treatment-seeking smokers (N= 20) following smoking satiety and again following 48 hours of nicotine abstinence...
February 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Vaughn R Steele, J Michael Maurer, Mohammad R Arbabshirani, Eric D Claus, Brandi C Fink, Vikram Rao, Vince D Calhoun, Kent A Kiehl
BACKGROUND: Successfully treating illicit drug use has become paramount, yet elusive. Devising specialized treatment interventions could increase positive outcomes, but it is necessary to identify risk factors of poor long-term outcomes to develop specialized, efficacious treatments. We investigated whether functional network connectivity (FNC) measures were predictive of substance abuse treatment completion using machine learning pattern classification of functional magnetic resonance imaging data...
February 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
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