Open access bioinformatics最新文献

Genome-Wide Mapping of Chromatin State of Mouse Forelimbs. 小鼠前肢染色质状态的全基因组定位。

Open access bioinformatics Pub Date : 2014-09-10 DOI: 10.2147/OAB.S59043

Diana Eng, Walter K Vogel, Nicholas S Flann, Michael K Gross, Chrissa Kioussi

{"title":"Genome-Wide Mapping of Chromatin State of Mouse Forelimbs.","authors":"Diana Eng, Walter K Vogel, Nicholas S Flann, Michael K Gross, Chrissa Kioussi","doi":"10.2147/OAB.S59043","DOIUrl":"https://doi.org/10.2147/OAB.S59043","url":null,"abstract":"Background: Cell types are defined at the molecular level during embryogenesis by a process called pattern formation and created by the selective utilization of combinations of sequence specific transcription factors. Developmental programs define the sets of genes that are available to each particular cell type, and real-time biochemical signaling interactions define the extent to which these sets are used at any given time and place. Gene expression is regulated through the integrated action of many cis-regulatory elements, including core promoters, enhancers, silencers, and insulators. The chromatin state in developing body parts provides a code to cellular populations that direct their cell fates. Chromatin profiling has been a method of choice for mapping regulatory sequences in cells that go through developmental transitions.Results: We used antibodies against histone H3 lysine 4 trimethylations (H3K4me3) a modification associated with promoters and open/active chromatin, histone H3 lysine 27 trimethylations (H3K27me3) associated with Polycomb-repressed regions and RNA polymerase II (Pol2) associated with transcriptional initiation to identify the chromatin state signature of the mouse forelimb during mid-gestation, at embryonic day 12 (E12). The families of genes marked included those related to transcriptional regulation and embryogenesis. One third of the marked genes were transcriptionally active while only a small fraction were bivalent marked. Sequence specific transcription factors that were activated were involved in cell specification including bone and muscle formation.Conclusion: Our results demonstrate that embryonic limb cells do not exhibit the plasticity of the ES cells but are rather programmed for a finer tuning for cell lineage specification.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"6 2014","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2014-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OAB.S59043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32926682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Vertebrate hepatic lipase genes and proteins: a review supported by bioinformatic studies. 脊椎动物肝脂肪酶基因和蛋白质:生物信息学研究支持的综述。

Open access bioinformatics Pub Date : 2011-04-22 DOI: 10.2147/OAB.S18401

Roger S Holmes, John L Vandeberg, Laura A Cox

{"title":"Vertebrate hepatic lipase genes and proteins: a review supported by bioinformatic studies.","authors":"Roger S Holmes, John L Vandeberg, Laura A Cox","doi":"10.2147/OAB.S18401","DOIUrl":"https://doi.org/10.2147/OAB.S18401","url":null,"abstract":"Hepatic lipase (gene: LIPC; enzyme: HL; E.C.3.1.1.3) is one of three members of the triglyceride lipase family that contributes to vascular lipoprotein degradation and serves a dual role in triglyceride hydrolysis and in facilitating receptor-mediated lipoprotein uptake into the liver. Amino acid sequences, protein structures, and gene locations for vertebrate LIPC (or Lipc for mouse and rat) genes and proteins were sourced from previous reports and vertebrate genome databases. Lipc was distinct from other neutral lipase genes (Lipg encoding endothelial lipase and Lpl encoding lipoprotein lipase [LPL]) and was located on mouse chromosome 9 with nine coding exons on the negative strand. Exon 9 of human LIPC and mouse and rat Lipc genes contained \"stop codons\" in different positions, causing changes in C-termini length. Vertebrate HL protein subunits shared 58%-97% sequence identities, including active, signal peptide, disulfide bond, and N-glycosylation sites, as well as proprotein convertase (\"hinge\") and heparin binding regions. Predicted secondary and tertiary structures revealed similarities with the three-dimensional structure reported for horse and human pancreatic lipases. Potential sites for regulating LIPC gene expression included CpG islands near the 5″-untranslated regions of the mouse and rat LIPC genes. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate LIPC gene family with other neutral triglyceride lipase gene families (LIPG and LPL). We conclude that the triglyceride lipase ancestral gene for vertebrate neutral lipase genes (LIPC, LIPG, and LPL) predated the appearance of fish during vertebrate evolution.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":" ","pages":"85-95"},"PeriodicalIF":0.0,"publicationDate":"2011-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OAB.S18401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40156222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

A Predictive Tool for Foreign Body Fibrotic Reactions Using 2-Dimensional Computational Model. 利用二维计算模型预测异物纤维化反应的工具

Open access bioinformatics Pub Date : 2011-01-01 DOI: 10.2147/OAB.S14254

Jianzhong Su, Michail Todorov, Humberto Perez Gonzales, Larrissa Perkins, Hristo Kojouharov, Hong Weng, Liping Tang

{"title":"A Predictive Tool for Foreign Body Fibrotic Reactions Using 2-Dimensional Computational Model.","authors":"Jianzhong Su, Michail Todorov, Humberto Perez Gonzales, Larrissa Perkins, Hristo Kojouharov, Hong Weng, Liping Tang","doi":"10.2147/OAB.S14254","DOIUrl":"10.2147/OAB.S14254","url":null,"abstract":"It is well established that implanted medical devices often trigger immunological and inflammatory reactions. Such foreign body-mediated tissue responses may result in fibrotic tissue formation surrounding the implants. Despite of intensive research in the area of wound healing, few methods are currently available to systematically predict the quantitative behavior of the complex system of multiple cells, proteins and enzymes during foreign body-associated fibrotic reactions. This study introduces a kinetics-based predictive tool to analyze outcomes of reactions of various cells/proteins and biochemical processes and to understand transient behavior during the entire implant healing period up to several months in time. A computational model in two spatial dimensions is constructed to investigate the time dynamics as well as spatial variation of fibrotic reaction kinetics. Our results have shown that this model can be used to predict many features in a systematic way and also complement the traditional immunological methodology by experiments or empirical data predictions.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"2011 3","pages":"19-35"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151680/pdf/nihms314165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29928939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microarray oligonucleotide probe designer (MOPeD): A web service. 微阵列寡核苷酸探针设计器(mopp):一个web服务。

Open access bioinformatics Pub Date : 2010-11-01 DOI: 10.2147/OAB.S13741

Viren C Patel, Kajari Mondal, Amol Carl Shetty, Vanessa L Horner, Jirair K Bedoyan, Donna Martin, Tamara Caspary, David J Cutler, Michael E Zwick

{"title":"Microarray oligonucleotide probe designer (MOPeD): A web service.","authors":"Viren C Patel, Kajari Mondal, Amol Carl Shetty, Vanessa L Horner, Jirair K Bedoyan, Donna Martin, Tamara Caspary, David J Cutler, Michael E Zwick","doi":"10.2147/OAB.S13741","DOIUrl":"https://doi.org/10.2147/OAB.S13741","url":null,"abstract":"Methods of genomic selection that combine high-density oligonucleotide microarrays with next-generation DNA sequencing allow investigators to characterize genomic variation in selected portions of complex eukaryotic genomes. Yet choosing which specific oligonucleotides to be use can pose a major technical challenge. To address this issue, we have developed a software package called MOPeD (Microarray Oligonucleotide Probe Designer), which automates the process of designing genomic selection microarrays. This web-based software allows individual investigators to design custom genomic selection microarrays optimized for synthesis with Roche NimbleGen's maskless photolithography. Design parameters include uniqueness of the probe sequences, melting temperature, hairpin formation, and the presence of single nucleotide polymorphisms. We generated probe databases for the human, mouse, and rhesus macaque genomes and conducted experimental validation of MOPeD-designed microarrays in human samples by sequencing the human X chromosome exome, where relevant sequence metrics indicated superior performance relative to a microarray designed by the Roche NimbleGen proprietary algorithm. We also performed validation in the mouse to identify known mutations contained within a 487-kb region from mouse chromosome 16, the mouse chromosome 16 exome (1.7 Mb), and the mouse chromosome 12 exome (3.3 Mb). Our results suggest that the open source MOPeD software package and website (http://moped.genetics.emory.edu/) will make a valuable resource for investigators in their sequence-based studies of complex eukaryotic genomes.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"2 2010","pages":"145-155"},"PeriodicalIF":0.0,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OAB.S13741","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29719120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Computational methods for the identification of microRNA targets. microRNA靶标鉴定的计算方法。

Open access bioinformatics Pub Date : 2010-05-01 DOI: 10.2147/OAB.S6902

Yang Dai, Xiaofeng Zhou

引用次数: 41

Analysis of Botulinum Neurotoxin Serotype A Metalloprotease Inhibitors: Analogs of a Chemotype for Therapeutic Development in the Context of a Three-Zone Pharmacophore. 肉毒杆菌神经毒素血清型 A 金属蛋白酶抑制剂分析：三区药理学背景下用于治疗开发的化学型类似物。

Open access bioinformatics Pub Date : 2010-04-01 DOI: 10.2147/OAB.S7251

James C Burnett, Bing Li, Ramdas Pai, Steven C Cardinale, Michelle M Butler, Norton P Peet, Donald Moir, Sina Bavari, Terry Bowlin

{"title":"Analysis of Botulinum Neurotoxin Serotype A Metalloprotease Inhibitors: Analogs of a Chemotype for Therapeutic Development in the Context of a Three-Zone Pharmacophore.","authors":"James C Burnett, Bing Li, Ramdas Pai, Steven C Cardinale, Michelle M Butler, Norton P Peet, Donald Moir, Sina Bavari, Terry Bowlin","doi":"10.2147/OAB.S7251","DOIUrl":"10.2147/OAB.S7251","url":null,"abstract":"Botulinum neurotoxins (BoNTs), and in particular serotype A, are the most poisonous of known biological substances, and are responsible for the flaccid paralysis of the disease state botulism. Because of the extreme toxicity of these enzymes, BoNTs are considered highest priority biothreat agents. To counter BoNT serotype A (BoNT/A) poisoning, the discovery and development of small molecule, drug-like inhibitors as post-intoxication therapeutic agents has been/is being pursued. Specifically, we are focusing on inhibitors of the BoNT/A light chain (LC) (ie, a metalloprotease) subunit, since such compounds can enter neurons and provide post-intoxication protection of the enzyme target substrate. To aid/facilitate this drug development effort, a pharmacophore for inhibition of the BoNT/A LC subunit was previously developed, and is continually being refined via the incorporation of novel and diverse inhibitor chemotypes. Here, we describe several analogs of a promising therapeutic chemotype in the context of the pharmacophore for BoNT/A LC inhibition. Specifically, we describe: 1) the pharmacophoric 'fits' of the analogs and how these 'fits' rationalize the in vitro inhibitory potencies of the analogs and 2) pharmacophore refinement via the inclusion of new components from the most potent of the presented analogs.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"2010 2","pages":"11-18"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2983112/pdf/nihms233188.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29490507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Balancing false discovery and false negative rates in selection of differentially expressed genes in microarrays. 平衡微阵列中差异表达基因选择中的错误发现和假阴性率。

Open access bioinformatics Pub Date : 2010-02-01 DOI: 10.2147/OAB.S7181

Byung S Park, Motomi Mori

{"title":"Balancing false discovery and false negative rates in selection of differentially expressed genes in microarrays.","authors":"Byung S Park, Motomi Mori","doi":"10.2147/OAB.S7181","DOIUrl":"https://doi.org/10.2147/OAB.S7181","url":null,"abstract":"Genome-wide mRNA expression profiling using microarrays is widely available today, yet analysis and interpretation of the resulting high dimensional data continue to be a challenge for biomedical scientists. In a typical microarray experiment, the number of biological samples is quite modest compared with the number of genes on a microarray, and a probability of falsely declaring differential expression is unacceptably high without any adjustment for multiple comparisons. However, a stringent multiple comparison procedure can lead to an unacceptably high false negative rate, potentially missing a large fraction of truly differentially expressed genes. In this paper we propose a new \"balancing factor score\" (BFS) method for identifying a set of differentially expressed genes. The BFS method combines a traditional P value criterion with any other informative factors (referred to as balancing factors) that may help to identify differentially expressed genes. We evaluate the performance of the BFS method when the observed fold change is used as a balancing factor in a simulation study and show that the BFS method can substantially reduce the false negative rate while maintaining a reasonable false discovery rate.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"2010 2","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2010-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OAB.S7181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30227016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Computational studies of NMDA receptors: differential effects of neuronal activity on efficacy of competitive and non-competitive antagonists. NMDA受体的计算研究:竞争性和非竞争性拮抗剂对神经元活性的不同影响。

Open access bioinformatics Pub Date : 2010-01-01 DOI: 10.2147/OAB.S7246

Nicolas Ambert, Renaud Greget, Olivier Haeberlé, Serge Bischoff, Theodore W Berger, Jean-Marie Bouteiller, Michel Baudry

{"title":"Computational studies of NMDA receptors: differential effects of neuronal activity on efficacy of competitive and non-competitive antagonists.","authors":"Nicolas Ambert, Renaud Greget, Olivier Haeberlé, Serge Bischoff, Theodore W Berger, Jean-Marie Bouteiller, Michel Baudry","doi":"10.2147/OAB.S7246","DOIUrl":"https://doi.org/10.2147/OAB.S7246","url":null,"abstract":"N-Methyl-D-Aspartate receptors (NMDARs) play important physiological as well as pathological roles in the central nervous system (CNS). While NMDAR competitive antagonists, such as D-2-Amino-5-Phosphopentanoic acid (AP5) have been shown to impair learning and memory, the non-competitive antagonist, memantine, is paradoxically beneficial in mild to moderate Alzheimer's disease (AD) patients. It has been proposed that differences in kinetic properties could account for antagonist functional differences. Here we present a new elaborated kinetic model of NMDARs that incorporates binding sites for the agonist (glutamate) and co-agonist (glycine), channel blockers, such as memantine and magnesium (Mg(2+)), as well as competitive antagonists. We first validated and optimized the parameters used in the model by comparing simulated results with a wide range of experimental data from the literature. We then evaluated the effects of stimulation frequency and membrane potential (Vm) on the characteristics of AP5 and memantine inhibition of NMDARs. Our results indicated that the inhibitory effects of AP5 were independent of Vm but decreased with increasing stimulation frequency. In contrast, memantine inhibitory effects decreased with both increasing Vm and stimulation frequency. They support the idea that memantine could provide tonic blockade of NMDARs under basal stimulation conditions without blocking their activation during learning. Moreover they underline the necessity of considering receptor kinetics and the value of the biosimulation approach to better understand mechanisms of drug action and to identify new ways of regulating receptor function.","PeriodicalId":89207,"journal":{"name":"Open access bioinformatics","volume":"2 ","pages":"113-125"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OAB.S7246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30185971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32