Advances and Applications in Bioinformatics and Chemistry最新文献

{"title":"Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site.","authors":"Manoj M Narayanan,&nbsp;Chandrasekhar B Nair,&nbsp;Shilpa K Sanjeeva,&nbsp;Pv Subba Rao,&nbsp;Phani K Pullela,&nbsp;Colin J Barrow","doi":"10.2147/AABC.S49503","DOIUrl":"https://doi.org/10.2147/AABC.S49503","url":null,"abstract":"<p><p>Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present. </p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"6 ","pages":"47-53"},"PeriodicalIF":0.0,"publicationDate":"2013-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S49503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31688701","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}

{"title":"Antigenic heterogeneity of capsid protein VP1 in foot-and-mouth disease virus (FMDV) serotype Asia 1.","authors":"S M Sabbir Alam,&nbsp;Ruhul Amin,&nbsp;Mohammed Ziaur Rahman,&nbsp;M Anwar Hossain,&nbsp;Munawar Sultana","doi":"10.2147/AABC.S49587","DOIUrl":"https://doi.org/10.2147/AABC.S49587","url":null,"abstract":"<p><p>Foot and mouth disease virus (FMDV), with its seven serotypes, is a highly contagious virus infecting mainly cloven-hoofed animals. The serotype Asia1 occurs mainly in Asian regions. An in-silico approach was taken to reveal the antigenic heterogeneities within the capsid protein VP1 of Asia1. A total of 47 VP1 sequences of Asia1 isolates from different countries of South Asian regions were selected, retrieved from database, and were aligned. The structure of VP1 protein was modeled using a homology modeling approach. Several antigenic sites were identified and mapped onto the three-dimensional protein structure. Variations at these antigenic sites were analyzed by calculating the protein variability index and finding mutation combinations. The data suggested that vaccine escape mutants have derived from only few mutations at several antigenic sites. Five antigenic peptides have been identified as the least variable epitopes, with just fewer amino acid substitutions. Only a limited number of serotype Asia1 antigenic variants were found to be circulated within the South Asian region. This emphasizes a possibility of formulating synthetic vaccines for controlling foot-and-mouth disease by Asia1 serotypes. </p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"6 ","pages":"37-46"},"PeriodicalIF":0.0,"publicationDate":"2013-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S49587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31688699","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}

{"title":"Approaches to the detection of recessive effects using next generation sequencing data from outbred populations.","authors":"David Curtis","doi":"10.2147/AABC.S44332","DOIUrl":"https://doi.org/10.2147/AABC.S44332","url":null,"abstract":"<p><p>Conventional methods to analyze genome-wide association studies and whole exome or whole genome sequencing studies would be prone to overlook variants which might exert a recessive effect on risk of disease, either as homozygotes or compound heterozygotes. It is plausible that such effects may be common even in outbred populations. An approach is described which is based on identifying a set of variants in a gene as being potentially of interest and then testing whether there is an excess of cases who are either homozygotes or complex heterozygotes for these variants. Methods based on departure from Hardy-Weinberg equilibrium are more powerful than those which compare cases to controls. However, linkage disequilibrium between variants can be difficult to deal with if phase is unknown. A simple approach for discarding variants apparently in strong linkage disequilibrium with others is proposed. The procedure is simple and quick to apply so can be used in the context of whole genome or exome sequencing studies and is implemented in the SCOREASSOC program. </p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"6 ","pages":"29-35"},"PeriodicalIF":0.0,"publicationDate":"2013-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S44332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31540525","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}

{"title":"Inferences on the biochemical and environmental regulation of universal stress proteins from Schistosomiasis parasites.","authors":"Andreas N Mbah,&nbsp;Ousman Mahmud,&nbsp;Omotayo R Awofolu,&nbsp;Raphael D Isokpehi","doi":"10.2147/AABC.S37191","DOIUrl":"https://doi.org/10.2147/AABC.S37191","url":null,"abstract":"<p><strong>Background: </strong>Human schistosomiasis is a freshwater snail-transmitted disease caused by parasitic flatworms of the Schistosoma genus. Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum are the three major species infecting humans. These parasites undergo a complex developmental life cycle, in which they encounter a plethora of environmental signals. The presence of genes encoding the universal stress protein (USP) domain in the genomes of Schistosoma spp. suggests these flatworms are equipped to respond to unfavorable conditions. Though data on gene expression is available for USP genes, their biochemical and environmental regulation are incompletely understood. The identification of additional regulatory molecules for Schistosoma. USPs, which may be present in the human, snail, or water environments, could also be useful for schistosomiasis interventions.</p><p><strong>Methods: </strong>We developed a protocol that includes a visual analytics stage to facilitate integration, visualization, and decision making, from the results of sequence analyses and data collection on a set of 13 USPs from S. mansoni and S. japonicum.</p><p><strong>Results: </strong>Multiple sequence alignment identified conserved sites that could be key residues regulating the function of USPs of the Schistosoma spp. Based on the consistency and completeness of sequence annotation, we prioritized for further research the gene for a 184-amino-acid-long USP that is present in the genomes of the three human-infecting Schistosoma spp. Calcium, zinc, and magnesium ions were predicted to interact with the protein product of the gene.</p><p><strong>Conclusion: </strong>Given that the initial effects of praziquantel on schistosomes include the influx of calcium ions, additional investigations are required to (1) functionally characterize the interactions of calcium ions with the amino acid residues of Schistosoma USPs; and (2) determine the transcriptional response of Schistosoma. USP genes to praziquantel. The data sets produced, and the visual analytics views that were developed, can be easily reused to develop new hypotheses.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"6 ","pages":"15-27"},"PeriodicalIF":0.0,"publicationDate":"2013-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S37191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31449870","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}

{"title":"Genetic and chemical knockdown: a complementary strategy for evaluating an anti-infective target.","authors":"Vasanthi Ramachandran,&nbsp;Ragini Singh,&nbsp;Xiaoyu Yang,&nbsp;Ragadeepthi Tunduguru,&nbsp;Subrat Mohapatra,&nbsp;Swati Khandelwal,&nbsp;Sanjana Patel,&nbsp;Santanu Datta","doi":"10.2147/AABC.S39198","DOIUrl":"https://doi.org/10.2147/AABC.S39198","url":null,"abstract":"<p><p>The equity of a drug target is principally evaluated by its genetic vulnerability with tools ranging from antisense- and microRNA-driven knockdowns to induced expression of the target protein. In order to upgrade the process of antibacterial target identification and discern its most effective type of inhibition, an in silico toolbox that evaluates its genetic and chemical vulnerability leading either to stasis or cidal outcome was constructed and validated. By precise simulation and careful experimentation using enolpyruvyl shikimate-3-phosphate synthase and its specific inhibitor glyphosate, it was shown that genetic knockdown is distinct from chemical knockdown. It was also observed that depending on the particular mechanism of inhibition, viz competitive, uncompetitive, and noncompetitive, the antimicrobial potency of an inhibitor could be orders of magnitude different. Susceptibility of Escherichia coli to glyphosate and the lack of it in Mycobacterium tuberculosis could be predicted by the in silico platform. Finally, as predicted and simulated in the in silico platform, the translation of growth inhibition to a cidal effect was able to be demonstrated experimentally by altering the carbon source from sorbitol to glucose.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"6 ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S39198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31241553","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}

{"title":"A rapid method for combined analysis of common and rare variants at the level of a region, gene, or pathway.","authors":"David Curtis","doi":"10.2147/AABC.S33049","DOIUrl":"https://doi.org/10.2147/AABC.S33049","url":null,"abstract":"<p><p>Previously described methods for the combined analysis of common and rare variants have disadvantages such as requiring an arbitrary classification of variants or permutation testing to assess statistical significance. Here we propose a novel method which implements a weighting scheme based on allele frequencies observed in both cases and controls. Because the test is unbiased, scores can be analyzed with a standard t-test. To test its validity we applied it to data for common, rare, and very rare variants simulated under the null hypothesis. To test its power we applied it to simulated data in which association was present, including data using the observed allele frequencies of common and rare variants in NOD2 previously reported in cases of Crohn's disease and controls. The method produced results that conformed well to those expected under the null hypothesis. It demonstrated more power to detect association when rare and common variants were analyzed jointly, the power further increasing when rare variants were assigned higher weights. 20,000 analyses of a gene containing 62 variants could be performed in 80 minutes on a laptop. This approach shows promise for the analysis of data currently emerging from genome wide sequencing studies.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"5 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S33049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30830176","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}

{"title":"Contact-based ligand-clustering approach for the identification of active compounds in virtual screening.","authors":"Alexey B Mantsyzov,&nbsp;Guillaume Bouvier,&nbsp;Nathalie Evrard-Todeschi,&nbsp;Gildas Bertho","doi":"10.2147/AABC.S30881","DOIUrl":"https://doi.org/10.2147/AABC.S30881","url":null,"abstract":"<p><p>Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Automatic analysis of poses using self-organizing maps (AuPosSOM) represents an alternative approach for the evaluation of docking results based on the clustering of compounds by the similarity of their contacts with the receptor. A scoring function was developed for the identification of the active compounds in the AuPosSOM clustered dataset. In addition, the AuPosSOM efficiency for the clustering of compounds and the identification of key contacts considered as important for its activity, were also improved. Benchmark tests for several targets revealed that together with the developed scoring function, AuPosSOM represents a good alternative to the energy-based scoring functions for the evaluation of docking results.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"5 ","pages":"61-79"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S30881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30968648","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}

{"title":"B-Pred, a structure based B-cell epitopes prediction server.","authors":"Luciano Giacò,&nbsp;Massimo Amicosante,&nbsp;Maurizio Fraziano,&nbsp;Pier Federico Gherardini,&nbsp;Gabriele Ausiello,&nbsp;Manuela Helmer-Citterich,&nbsp;Vittorio Colizzi,&nbsp;Andrea Cabibbo","doi":"10.2147/AABC.S30620","DOIUrl":"https://doi.org/10.2147/AABC.S30620","url":null,"abstract":"<p><p>The ability to predict immunogenic regions in selected proteins by in-silico methods has broad implications, such as allowing a quick selection of potential reagents to be used as diagnostics, vaccines, immunotherapeutics, or research tools in several branches of biological and biotechnological research. However, the prediction of antibody target sites in proteins using computational methodologies has proven to be a highly challenging task, which is likely due to the somewhat elusive nature of B-cell epitopes. This paper proposes a web-based platform for scoring potential immunological reagents based on the structures or 3D models of the proteins of interest. The method scores a protein's peptides set, which is derived from a sliding window, based on the average solvent exposure, with a filter on the average local model quality for each peptide. The platform was validated on a custom-assembled database of 1336 experimentally determined epitopes from 106 proteins for which a reliable 3D model could be obtained through standard modeling techniques. Despite showing poor sensitivity, this method can achieve a specificity of 0.70 and a positive predictive value of 0.29 by combining these two simple parameters. These values are slightly higher than those obtained with other established sequence-based or structure-based methods that have been evaluated using the same epitopes dataset. This method is implemented in a web server called B-Pred, which is accessible at http://immuno.bio.uniroma2.it/bpred. The server contains a number of original features that allow users to perform personalized reagent searches by manipulating the sliding window's width and sliding step, changing the exposure and model quality thresholds, and running sequential queries with different parameters. The B-Pred server should assist experimentalists in the rational selection of epitope antigens for a wide range of applications.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"5 ","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S30620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30830177","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}

{"title":"FDR-FET: an optimizing gene set enrichment analysis method.","authors":"Rui-Ru Ji,&nbsp;Karl-Heinz Ott,&nbsp;Roumyana Yordanova,&nbsp;Robert E Bruccoleri","doi":"10.2147/AABC.S15840","DOIUrl":"https://doi.org/10.2147/AABC.S15840","url":null,"abstract":"<p><p>Gene set enrichment analysis for analyzing large profiling and screening experiments can reveal unifying biological schemes based on previously accumulated knowledge represented as \"gene sets\". Most of the existing implementations use a fixed fold-change or P value cutoff to generate regulated gene lists. However, the threshold selection in most cases is arbitrary, and has a significant effect on the test outcome and interpretation of the experiment. We developed a new gene set enrichment analysis method, ie, FDR-FET, which dynamically optimizes the threshold choice and improves the sensitivity and selectivity of gene set enrichment analysis. The procedure translates experimental results into a series of regulated gene lists at multiple false discovery rate (FDR) cutoffs, and computes the P value of the overrepresentation of a gene set using a Fisher's exact test (FET) in each of these gene lists. The lowest P value is retained to represent the significance of the gene set. We also implemented improved methods to define a more relevant global reference set for the FET. We demonstrate the validity of the method using a published microarray study of three protease inhibitors of the human immunodeficiency virus and compare the results with those from other popular gene set enrichment analysis algorithms. Our results show that combining FDR with multiple cutoffs allows us to control the error while retaining genes that increase information content. We conclude that FDR-FET can selectively identify significant affected biological processes. Our method can be used for any user-generated gene list in the area of transcriptome, proteome, and other biological and scientific applications.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"4 ","pages":"37-42"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AABC.S15840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29996574","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}

{"title":"MODENA: a multi-objective RNA inverse folding.","authors":"Akito Taneda","doi":"10.2147/aabc.s14335","DOIUrl":"https://doi.org/10.2147/aabc.s14335","url":null,"abstract":"<p><p>Artificially synthesized RNA molecules have recently come under study since such molecules have a potential for creating a variety of novel functional molecules. When designing artificial RNA sequences, secondary structure should be taken into account since functions of noncoding RNAs strongly depend on their structure. RNA inverse folding is a methodology for computationally exploring the RNA sequences folding into a user-given target structure. In the present study, we developed a multi-objective genetic algorithm, MODENA (Multi-Objective DEsign of Nucleic Acids), for RNA inverse folding. MODENA explores the approximate set of weak Pareto optimal solutions in the objective function space of 2 objective functions, a structure stability score and structure similarity score. MODENA can simultaneously design multiple different RNA sequences at 1 run, whose lowest free energies range from a very stable value to a higher value near those of natural counterparts. MODENA and previous RNA inverse folding programs were benchmarked with 29 target structures taken from the Rfam database, and we found that MODENA can successfully design 23 RNA sequences folding into the target structures; this result is better than those of the other benchmarked RNA inverse folding programs. The multi-objective genetic algorithm gives a useful framework for a functional biomolecular design. Executable files of MODENA can be obtained at http://rna.eit.hirosaki-u.ac.jp/modena/.</p>","PeriodicalId":53584,"journal":{"name":"Advances and Applications in Bioinformatics and Chemistry","volume":"4 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/aabc.s14335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29996571","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}