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biological regulatory network

Juan I Fuxman Bass, Carles Pons, Lucie Kozlowski, John S Reece-Hoyes, Shaleen Shrestha, Amy D Holdorf, Akihiro Mori, Chad L Myers, Albertha Jm Walhout
Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences...
October 24, 2016: Molecular Systems Biology
Doyeon Kim, You Me Sung, Jinman Park, Sukjun Kim, Jongkyu Kim, Junhee Park, Haeok Ha, Jung Yoon Bae, SoHui Kim, Daehyun Baek
The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs...
October 24, 2016: Nature Genetics
William Chad Young, Adrian E Raftery, Ka Yee Yeung
Inferring gene regulatory networks is an important problem in systems biology. However, these networks can be hard to infer from experimental data because of the inherent variability in biological data as well as the large number of genes involved. We propose a fast, simple method for inferring regulatory relationships between genes from knockdown experiments in the NIH LINCS dataset by calculating posterior probabilities, incorporating prior information. We show that the method is able to find previously identified edges from TRANSFAC and JASPAR and discuss the merits and limitations of this approach...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
Jianjun Niu, Yong Lin, Pingguo Liu, Yiwen Yu, Chenghao Su, Xiaomin Wang
Long non-coding RNAs are involved with development and progression of cancer, and the advance of microarray technology allows the researchers to investigate the complete expression profile of lncRNA in various kinds of sample. We enrolled 5 male primary HCC cases with chronic HBV infection and the HCC and normal tissues have been obtained during the resection surgery. After total RNA extraction, the lncRNA microarray analysis was conducted to determine the lncRNA and mRNA expression signals. 612 lncRNAs and 1,064 mRNAs were significantly up-regulated in HCC tissue while 656 lncRNAs and 1,532 mRNAs were down-regulated in HCC tissues...
October 18, 2016: Oncotarget
Yajie Hu, Jie Song, Longding Liu, Jing Li, Beibei Tang, Jingjing Wang, Xiaolong Zhang, Ying Zhang, Lichun Wang, Yun Liao, Zhanlong He, Qihan Li
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant pathogens of hand, foot, and mouth disease (HFMD). Although these viruses exhibit genetic homology, the clinical manifestations caused by the two viruses have some discrepancies. In addition, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections. Here, we focused on differences in miRNA expression patterns in rhesus monkey peripheral blood mononuclear cells (PBMCs) infected with EV71 and CA16 at various time points using high-throughput sequencing...
October 17, 2016: International Journal of Biochemistry & Cell Biology
Xue Jiang, Lichun Feng, Baoqiang Dai, Liping Li, Weiwei Lu
INTRODUCTION: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. OBJECTIVE: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. METHODS: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package...
September 26, 2016: Brazilian Journal of Otorhinolaryngology
Kevin A McGoff, Xin Guo, Anastasia Deckard, Christina M Kelliher, Adam R Leman, Lauren J Francey, John B Hogenesch, Steven B Haase, John L Harer
We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, sizes, and degrees of complexity. Moreover, we demonstrate its ability to incorporate biological prior information and make informative predictions on a well-characterized in vivo system using data from budding yeast that have been synchronized in the cell cycle...
October 19, 2016: Genome Biology
Daifeng Wang, Fei He, Sergei Maslov, Mark Gerstein
Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution...
October 2016: PLoS Computational Biology
Qiangfeng Wang, Huanxia Yang, Lingjiao Wu, Jian Yao, Xiaohua Meng, Han Jiang, Cheng Xiao, Fusheng Wu
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription PCR (qRT-PCR) were used to detect and verify, respectively, changes to the transcriptomic profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathological characteristics was analysed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs...
October 19, 2016: Thyroid: Official Journal of the American Thyroid Association
Shazia Nafis, Kalaiarasan Ponnusamy, Mohammad Husain, R K Brojen Singh, Rameshwar N K Bamezai
An experimentally validated set of apoptosis-regulatory proteins was subjected to network analysis, depicting a scale-free hierarchical fractal network. The power-law distribution of the various topological properties of the network revealed the fractal nature of the network, a signature of self-organization of the network where the network maintained the democratic constitution of nodes at various levels and showed the absence of the centrality-lethality control system. Even though network breakdown under the absence of the centrality-lethality rule of hub removal did not happen, the change in the topological properties of the network could be observed...
October 18, 2016: Molecular BioSystems
Jeganathan Manivannan, Manjunath Prashanth, Venkatesan Saravana Kumar, Manickaraj Shairam, Jayachandran Subburaj
Since there is no precise therapy for treating vascular calcification by directly targeting the vascular wall, we aim to unveil novel drug targets through mining the molecular effect of a high phosphate environment on vascular cells through computational methods. Here, we hypothesize that manipulation of the vascular pathogenic network by small molecule therapeutics predicted from prior knowledge might offer great promise. With this, we intend to understand the publicly available transcriptomic data of vascular smooth muscle cells and endothelial cells exposed to the high phosphate induced vascular calcification milieu and to re-examine the above published experiments for reasons different from those examined in the previous studies through multilevel systems biological understanding...
October 18, 2016: Molecular BioSystems
Federica Parodi, Roberta Carosio, Marco Ragusa, Cinzia Di Pietro, Marco Maugeri, Davide Barbagallo, Fabio Sallustio, Giorgio Allemanni, Maria Pia Pistillo, Ida Casciano, Alessandra Forlani, Francesco P Schena, Michele Purrello, Massimo Romani, Barbara Banelli
In neuroblastoma, the epigenetic landscape is more profoundly altered in aggressive compared to lower grade tumors and the concomitant hypermethylation of many genes, defined as "methylator phenotype", has been associated with poor outcome. DNA methylation can interfere with gene expression acting at distance through the methylation or demethylation of the regulatory regions of miRNAs. The multiplicity of miRNA targets may result in the simultaneous alteration of many biological pathways like cell proliferation, apoptosis, migration and differentiation...
October 15, 2016: Biochimica et Biophysica Acta
Shanshan Xu, Lanlan Dong, Yingying Shi, Liujun Chen, Peipei Yuan, Shuang Wang, Zhi Li, Yan Sun, Song Han, Jun Yin, Biwen Peng, Xiaohua He, Wanhong Liu
Human foamy virus (HFV) is a complex and unique retrovirus with the longest genomes among retroviruses used as vectors for gene therapy. Long non-coding RNAs (lncRNAs) are regarded as key regulators that involved in diverse biological processes during viral infection. However, the role of lncRNAs in HFV infection remains unknown. In this study, we utilized next-generation sequencing to first characterize lncRNAs in 293T cells after HFV infection, evaluating length distribution, exon number distribution, volcano picture and lncRNA class distribution...
October 18, 2016: AIDS Research and Human Retroviruses
Qin Wang, Katherine J Franz
Metal ions are essential for a wide range of physiological processes, but they can also be toxic if not appropriately regulated by a complex network of metal trafficking proteins. Intervention in cellular metal distribution with small-molecule or peptide chelating agents has promising therapeutic potential to harness metals to fight disease. Molecular outcomes associated with forming metal-chelate interactions in situ include altering the concentration and subcellular metal distribution, inhibiting metalloenzymes, enhancing the reactivity of a metal species to elicit a favorable biological response, or passivating the reactivity of a metal species to prevent deleterious reactivity...
October 17, 2016: Accounts of Chemical Research
Jing-Yi Li, Li-Li Zheng, Ting-Ting Wang, Min Hu
BACKGROUND: Melanoma is a type of cancer that develops from the pigment-containing cells. Until now, its pathological mechanisms remain largely unknown. The aim of this study was to identify metastasis-related microRNA (miRNAs) and gain an understanding of the biological functions in the metastasis of melanoma. METHODS: We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma, with key words of "melanoma", "miRNA", "microarray", and "gene expression profiling"...
2016: Chinese Medical Journal
P Zhang, L Tao, X Zeng, C Qin, S Y Chen, F Zhu, S Y Yang, Z R Li, W P Chen, Y Z Chen
The studies of biological, disease and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web-servers for computing network descriptors, but many descriptors are not covered including those used or useful for biological studies...
October 11, 2016: Journal of Molecular Biology
Kevin R Pilkiewicz, Michael L Mayo
The internal biochemical state of a cell is regulated by a vast transcriptional network that kinetically correlates the concentrations of numerous proteins. Fluctuations in protein concentration that encode crucial information about this changing state must compete with fluctuations caused by the noisy cellular environment in order to successfully transmit information across the network. Oftentimes, one protein must regulate another through a sequence of intermediaries, and conventional wisdom, derived from the data processing inequality of information theory, leads us to expect that longer sequences should lose more information to noise...
September 2016: Physical Review. E
Erica Sarchielli, Paolo Comeglio, Roberta Squecco, Lara Ballerini, Tommaso Mello, Giulia Guarnieri, Eglantina Idrizaj, Benedetta Mazzanti, Linda Vignozzi, Pasquale Gallina, Mario Maggi, Gabriella B Vannelli, Annamaria Morelli
CONTEXT: Previous studies have suggested that inflammatory pathways may impair central regulatory networks involving gonadotropin-releasing hormone (GnRH) neuron activity. Studies in humans are strongly hampered by the lack of human GnRH neuron cell lines. OBJECTIVE: To establish an in vitro model of GnRH neurons of human origin and analyze the effects of proinflammatory cytokines on their biological properties. Design, samples and treatments: The primary human fetal hypothalamic (hfHypo) cell cultures were isolated from brain of three 12 week-old fetuses...
October 13, 2016: Journal of Clinical Endocrinology and Metabolism
Archana Prabahar, Jeyakumar Natarajan
Autoimmune diseases (AIDs) are incurable but suppressible diseases whose molecular mechanisms are yet to be elucidated. In this work, we selected five systemic autoimmune diseases such as Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D), Inflammatory Bowel Disease (IBD), Autoimmune Thyroid Disease (ATD) and Systemic Lupus Erythematosus (SLE) and integrated their heterogeneous data such as miRNA, transcription factor (TF), target genes and protein-protein interactions involved in these AIDs to understand their roles at different functional levels of miRNA such as transcription initiation, gene regulatory network formation and post transcriptional regulation...
October 8, 2016: Journal of Immunological Methods
Atsushi Mochizuki
Modern biology has provided many examples of large networks describing the interactions between multiple species of bio-molecules. It is believed that the dynamics of molecular activities based on such networks are the origin of biological functions. On the other hand, we have a limited understanding for dynamics of molecular activity based on networks. To overcome this problem, we have developed two structural theories, by which the important aspects of the dynamical properties of the system are determined only from information on the network structure, without assuming other quantitative details...
2016: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
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