Bioinformatics: making large-scale science happen

Bionformatics is a rapidly evolving research field dedicated toanalyzing and managing biological data with computational resources. This paperaims to overview some of the processes and applications currently implementedat CCiT-UB¿s Bioinformatics Unit, focusing mainly on the areas of Genomics,Transcriptomics and Proteomics

Contamination of genomic databases by HIV-1 and its possible consequences. A study in Bioinformatics.

Peer-reviewed

Bioinformatics and HIV Latency.

Despite effective treatment, HIV is not completely eliminated from the infected organism because of the existence of viral reservoirs. A major reservoir consists of infected resting CD4+ T cells, mostly of memory type, that persist over time due to the stable proviral insertion and a long cellular lifespan. Resting cells do not produce viral particles and are protected from viral-induced cytotoxicity or immune killing. However, these latently infected cells can be reactivated by stochastic events or by external stimuli. The present review focuses on novel genome-wide technologies applied to the study of integration, transcriptome, and proteome characteristics and their recent contribution to the understanding of HIV latency.

BioSWR - Semantic Web services Registry for Bioinformatics

Article About the Authors Metrics Comments Related Content Abstract Introduction Functionality Implementation Discussion Acknowledgments Author Contributions References Reader Comments (0) Figures Abstract Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL). Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL). BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF) based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST) API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/​under the LGPL license.

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases.

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article.

Tools and data services registry: a community effort to document bioinformatics resources.

Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.

Structural bioinformatics study of cyclin-dependent kinases complexed with inhibitors

The present work describes molecular models for the binary complexes CDK9, CDK5 and CDK1 complexed with Flavopiridol and Roscovitine. These structural models indicate that the inhibitors strongly bind to the ATP-binding pocket of CDKs and the structural comparison with the complexes CDK2:Flavopiridol and CDK2:Roscovitine correlates the structural differences with differences in inhibition of these CDKs by the inhibitors. These structures open the possibility of testing new inhibitor families, in addition to new substituents for the already known lead structures such as flavones and adenine derivatives.

Cloning, bioinformatics analysis, and expression of the dust mite allergen Der f 5 of Dermatophagoides farinae

Crude extracts of house dust mites are used clinically for diagnosis and immunotherapy of allergic diseases, including bronchial asthma, perennial rhinitis, and atopic dermatitis. However, crude extracts are complexes with non-allergenic antigens and lack effective concentrations of important allergens, resulting in several side effects. Dermatophagoides farinae (Hughes; Acari: Pyroglyphidae) is one of the predominant sources of dust mite allergens, which has more than 30 groups of allergen. The cDNA coding for the group 5 allergen of D. farinae from China was cloned, sequenced and expressed. According to alignment using the VECTOR NTI 9.0 software, there were eight mismatched nucleotides in five cDNA clones resulting in seven incompatible amino acid residues, suggesting that the Der f 5 allergen might have sequence polymorphism. Bioinformatics analysis revealed that the matured Der f 5 allergen has a molecular mass of 13604.03 Da, a theoretical pI of 5.43 and is probably hydrophobic and cytoplasmic. Similarities in amino acid sequences between Der f 5 and allergens of other domestic mite species, viz. Der p 5, Blo t 5, Sui m 5, and Lep d 5, were 79, 48, 53, and 37%, respectively. Phylogenetic analysis indicated that Der f 5 and Der p 5 clustered together. Blo t 5 and Ale o 5 also clustered together, although Blomia tropicalis and Aleuroglyphus ovatus belong to different mite families, viz. Echimyopodidae and Acaridae, respectively.

Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome

In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression.

From protein structure to function with bioinformatics

It has long been known that amino acids are the building blocks for proteins and govern their folding into specific three-dimensional structures. However, the details of this process are still unknown and represent one of the main problems in structural bioinformatics, which is a highly active research area with the focus on the prediction of three-dimensional structure and its relationship to protein function. The protein structure prediction procedure encompasses several different steps from searches and analyses of sequences and structures, through sequence alignment to the creation of the structural model. Careful evaluation and analysis ultimately results in a hypothetical structure, which can be used to study biological phenomena in, for example, research at the molecular level, biotechnology and especially in drug discovery and development. In this thesis, the structures of five proteins were modeled with templatebased methods, which use proteins with known structures (templates) to model related or structurally similar proteins. The resulting models were an important asset for the interpretation and explanation of biological phenomena, such as amino acids and interaction networks that are essential for the function and/or ligand specificity of the studied proteins. The five proteins represent different case studies with their own challenges like varying template availability, which resulted in a different structure prediction process. This thesis presents the techniques and considerations, which should be taken into account in the modeling procedure to overcome limitations and produce a hypothetical and reliable three-dimensional structure. As each project shows, the reliability is highly dependent on the extensive incorporation of experimental data or known literature and, although experimental verification of in silico results is always desirable to increase the reliability, the presented projects show that also the experimental studies can greatly benefit from structural models. With the help of in silico studies, the experiments can be targeted and precisely designed, thereby saving both money and time. As the programs used in structural bioinformatics are constantly improved and the range of templates increases through structural genomics efforts, the mutual benefits between in silico and experimental studies become even more prominent. Hence, reliable models for protein three-dimensional structures achieved through careful planning and thoughtful executions are, and will continue to be, valuable and indispensable sources for structural information to be combined with functional data.

How to build a bioinformatics service in a year

Introduction: Biomedical scientists need to choose among hundreds of publicly available bioinformatics applications, tools, and databases. Librarian challenges include raising awareness to valuable resources, as well as providing support in finding and evaluating specific resources. Our objective is to implement an education program in bioinformatics similar to those offered in other North American academic libraries. Description: Our initial target clientele included four research departments of the Faculty of Medicine at Universite´ de Montréal. In January 2010, I attended two departmental meetings and interviewed a few stakeholders in order to propose a basic bioinformatics service: one-to-one consultations and a workshop on NCBI databases. The response was favourable. The workshop was thus offered once a month during the Winter and Fall semesters, and participants were invited to evaluate the workshop via an online survey. In addition, a bioinformatics subject guide was launched on the library’s website in December 2010. Outcomes: One hundred and two participants attended one of the nine NCBI workshops offered in 2010; most were graduate students (74%). The survey’s response rate was 54%. A majority of respondents thought that the bioinformatics resources featured in the workshop were relevant (95%) and that the difficulty level of exercises was appropriate (84%). Respondents also thought that their future information searches would be more efficient (93%) and that the workshop should be integrated in a course (78%). Furthermore, five bioinformatics-related reference questions were answered and two one-to-one consultations with students were performed. Discussion: The success of our bioinformatics service is growing. Future directions include extending the service to other biomedical departments, integrating the workshop in an undergraduate course, promoting the subject guide to other francophone universities, and creating a bioinformatics blog that would feature specific databases, news, and library resources.

Structural bioinformatics analysis of the family of human ubiquitin-specific proteases

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Assessment of meat authenticity using bioinformatics, targeted peptide biomarkers and high-resolution mass spectrometry

In recent years, we observed a significant increase of food fraud ranging from false label claims to the use of additives and fillers to increase profitability. Recently in 2013, horse and pig DNA were detected in beef products sold from several retailers. Mass spectrometry has become the workhorse in protein research and the detection of marker proteins could serve for both animal species and tissue authentication. Meat species authenticity will be performed using a well defined proteogenomic annotation, carefully chosen surrogate tryptic peptides and analysis using a hybrid quadrupole-Orbitrap mass spectrometer. Selected mammalian meat samples were homogenized, proteins were extracted and digested with trypsin. The samples were analyzed using a high-resolution mass spectrometer. The chromatography was achieved using a 30 minutes linear gradient along with a BioBasic C8 100 × 1 mm column at a flow rate of 75 µL/min. The mass spectrometer was operated in full-scan high resolution and accurate mass. MS/MS spectra were collected for selected proteotypic peptides. Muscular proteins were methodically analyzed in silico in order to generate tryptic peptide mass lists and theoretical MS/MS spectra. Following a comprehensive bottom-up proteomic analysis, we were able to detect and identify a proteotypic myoglobin tryptic peptide [120-134] for each species with observed m/z below 1.3 ppm compared to theoretical values. Moreover, proteotypic peptides from myosin-1, myosin-2 and -hemoglobin were also identified. This targeted method allowed a comprehensive meat speciation down to 1% (w/w) of undesired product.

Bioinformatics & Operational Research

Challenges for Web Science - applications in Bio & OR