89 results on '"C Victor Jongeneel"'
Search Results
2. Knowledge-guided analysis of 'omics' data using the KnowEnG cloud platform.
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Charles Blatti, Amin Emad, Matthew J Berry, Lisa Gatzke, Milt Epstein, Daniel Lanier, Pramod Rizal, Jing Ge, Xiaoxia Liao, Omar Sobh, Mike Lambert, Corey S Post, Jinfeng Xiao, Peter Groves, Aidan T Epstein, Xi Chen, Subhashini Srinivasan, Erik Lehnert, Krishna R Kalari, Liewei Wang, Richard M Weinshilboum, Jun S Song, C Victor Jongeneel, Jiawei Han, Umberto Ravaioli, Nahil Sobh, Colleen B Bushell, and Saurabh Sinha
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Biology (General) ,QH301-705.5 - Abstract
We present Knowledge Engine for Genomics (KnowEnG), a free-to-use computational system for analysis of genomics data sets, designed to accelerate biomedical discovery. It includes tools for popular bioinformatics tasks such as gene prioritization, sample clustering, gene set analysis, and expression signature analysis. The system specializes in "knowledge-guided" data mining and machine learning algorithms, in which user-provided data are analyzed in light of prior information about genes, aggregated from numerous knowledge bases and encoded in a massive "Knowledge Network." KnowEnG adheres to "FAIR" principles (findable, accessible, interoperable, and reuseable): its tools are easily portable to diverse computing environments, run on the cloud for scalable and cost-effective execution, and are interoperable with other computing platforms. The analysis tools are made available through multiple access modes, including a web portal with specialized visualization modules. We demonstrate the KnowEnG system's potential value in democratization of advanced tools for the modern genomics era through several case studies that use its tools to recreate and expand upon the published analysis of cancer data sets.
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- 2020
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3. Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network.
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C Victor Jongeneel, Ovokeraye Achinike-Oduaran, Ezekiel Adebiyi, Marion Adebiyi, Seun Adeyemi, Bola Akanle, Shaun Aron, Efejiro Ashano, Hocine Bendou, Gerrit Botha, Emile Chimusa, Ananyo Choudhury, Ravikiran Donthu, Jenny Drnevich, Oluwadamila Falola, Christopher J Fields, Scott Hazelhurst, Liesl Hendry, Itunuoluwa Isewon, Radhika S Khetani, Judit Kumuthini, Magambo Phillip Kimuda, Lerato Magosi, Liudmila Sergeevna Mainzer, Suresh Maslamoney, Mamana Mbiyavanga, Ayton Meintjes, Danny Mugutso, Phelelani Mpangase, Richard Munthali, Victoria Nembaware, Andrew Ndhlovu, Trust Odia, Adaobi Okafor, Olaleye Oladipo, Sumir Panji, Venesa Pillay, Gloria Rendon, Dhriti Sengupta, and Nicola Mulder
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Biology (General) ,QH301-705.5 - Abstract
The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so.
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- 2017
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4. Network-guided analysis of genes with altered somatic copy number and gene expression reveals pathways commonly perturbed in metastatic melanoma.
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Armand Valsesia, Donata Rimoldi, Danielle Martinet, Mark Ibberson, Paola Benaglio, Manfredo Quadroni, Patrice Waridel, Muriel Gaillard, Mireille Pidoux, Blandine Rapin, Carlo Rivolta, Ioannis Xenarios, Andrew J G Simpson, Stylianos E Antonarakis, Jacques S Beckmann, C Victor Jongeneel, Christian Iseli, and Brian J Stevenson
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Medicine ,Science - Abstract
Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression ('SCNA-genes') in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer.
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- 2011
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5. Indexing strategies for rapid searches of short words in genome sequences.
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Christian Iseli, Giovanna Ambrosini, Philipp Bucher, and C Victor Jongeneel
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Medicine ,Science - Abstract
Searching for matches between large collections of short (14-30 nucleotides) words and sequence databases comprising full genomes or transcriptomes is a common task in biological sequence analysis. We investigated the performance of simple indexing strategies for handling such tasks and developed two programs, fetchGWI and tagger, that index either the database or the query set. Either strategy outperforms megablast for searches with more than 10,000 probes. FetchGWI is shown to be a versatile tool for rapidly searching multiple genomes, whose performance is limited in most cases by the speed of access to the filesystem. We have made publicly available a Web interface for searching the human, mouse, and several other genomes and transcriptomes with oligonucleotide queries.
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- 2007
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6. Developing reproducible bioinformatics analysis workflows for heterogeneous computing environments to support African genomics
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Shakuntala Baichoo, Yassine Souilmi, Sumir Panji, Gerrit Botha, Ayton Meintjes, Scott Hazelhurst, Hocine Bendou, Eugene de Beste, Phelelani T. Mpangase, Oussema Souiai, Mustafa Alghali, Long Yi, Brian D. O’Connor, Michael Crusoe, Don Armstrong, Shaun Aron, Fourie Joubert, Azza E. Ahmed, Mamana Mbiyavanga, Peter van Heusden, Lerato E. Magosi, Jennie Zermeno, Liudmila Sergeevna Mainzer, Faisal M. Fadlelmola, C. Victor Jongeneel, and Nicola Mulder
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Workflows ,Pipeline ,Bioinformatics ,Africa ,Genomics ,Docker ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background The Pan-African bioinformatics network, H3ABioNet, comprises 27 research institutions in 17 African countries. H3ABioNet is part of the Human Health and Heredity in Africa program (H3Africa), an African-led research consortium funded by the US National Institutes of Health and the UK Wellcome Trust, aimed at using genomics to study and improve the health of Africans. A key role of H3ABioNet is to support H3Africa projects by building bioinformatics infrastructure such as portable and reproducible bioinformatics workflows for use on heterogeneous African computing environments. Processing and analysis of genomic data is an example of a big data application requiring complex interdependent data analysis workflows. Such bioinformatics workflows take the primary and secondary input data through several computationally-intensive processing steps using different software packages, where some of the outputs form inputs for other steps. Implementing scalable, reproducible, portable and easy-to-use workflows is particularly challenging. Results H3ABioNet has built four workflows to support (1) the calling of variants from high-throughput sequencing data; (2) the analysis of microbial populations from 16S rDNA sequence data; (3) genotyping and genome-wide association studies; and (4) single nucleotide polymorphism imputation. A week-long hackathon was organized in August 2016 with participants from six African bioinformatics groups, and US and European collaborators. Two of the workflows are built using the Common Workflow Language framework (CWL) and two using Nextflow. All the workflows are containerized for improved portability and reproducibility using Docker, and are publicly available for use by members of the H3Africa consortium and the international research community. Conclusion The H3ABioNet workflows have been implemented in view of offering ease of use for the end user and high levels of reproducibility and portability, all while following modern state of the art bioinformatics data processing protocols. The H3ABioNet workflows will service the H3Africa consortium projects and are currently in use. All four workflows are also publicly available for research scientists worldwide to use and adapt for their respective needs. The H3ABioNet workflows will help develop bioinformatics capacity and assist genomics research within Africa and serve to increase the scientific output of H3Africa and its Pan-African Bioinformatics Network.
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- 2018
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7. Efficient and Scalable Workflows for Genomic Analyses.
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Subho S. Banerjee, Arjun P. Athreya, Liudmila S. Mainzer, C. Victor Jongeneel, Wen-mei W. Hwu, Zbigniew T. Kalbarczyk, and Ravishankar K. Iyer
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- 2016
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8. KnowEnG: a knowledge engine for genomics.
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Saurabh Sinha, Jun Song, Richard M. Weinshilboum, C. Victor Jongeneel, and Jiawei Han 0001
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- 2015
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9. Modeling sequencing errors by combining Hidden Markov models.
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Claudio Lottaz, Christian Iseli, C. Victor Jongeneel, and Philipp Bucher
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- 2003
10. ESTScan: A Program for Detecting, Evaluating, and Reconstructing Potential Coding Regions in EST Sequences.
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Christian Iseli, C. Victor Jongeneel, and Philipp Bucher
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- 1999
11. The M-Coffee web server: a meta-method for computing multiple sequence alignments by combining alternative alignment methods.
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Sébastien Moretti, Fabrice Armougom, Iain M. Wallace, Desmond G. Higgins, C. Victor Jongeneel, and Cédric Notredame
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- 2007
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12. MyHits: improvements to an interactive resource for analyzing protein sequences.
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Marco Pagni, Vassilios Ioannidis, Lorenzo Cerutti, Monique Zahn-Zabal, C. Victor Jongeneel, Jörg Hau, Olivier Martin 0002, Dmitri Kuznetsov, and Laurent Falquet
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- 2007
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13. A View on Genomic Medicine Activities in Africa: Implications for Policy
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C. Victor Jongeneel, Maritha J. Kotze, Archana Bhaw-Luximon, Faisal M. Fadlelmola, Yasmina J. Fakim, Yosr Hamdi, Samar Kamal Kassim, Judit Kumuthini, Victoria Nembaware, Fouzia Radouani, Nicki Tiffin, and Nicola Mulder
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Genetics ,Molecular Medicine ,Genetics (clinical) - Abstract
Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine. We discuss how the information gathered in the survey could instruct the policies of African institutions seeking to implement precision, and more specifically, genomic medicine approaches in their health care systems in the following areas: 1) Prioritization of infrastructures. 2) Need for translational research. 3) Information dissemination to potential users. 4) Training programs for specialized personnel. 5) Engaging political stakeholders and the public. A checklist with key requirements to assess readiness for implementation of genomic medicine programs is provided to guide the process from scientific discovery to clinical application.
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- 2021
14. MyHits: a new interactive resource for protein annotation and domain identification.
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Marco Pagni, Vassilios Ioannidis, Lorenzo Cerutti, Monique Zahn-Zabal, C. Victor Jongeneel, and Laurent Falquet
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- 2004
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15. trEST, trGEN and Hits: access to databases of predicted protein sequences.
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Marco Pagni, Christian Iseli, Thomas Junier, Laurent Falquet, C. Victor Jongeneel, and Philipp Bucher
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- 2001
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16. Making Sense of Score Statistics for Sequence Alignments.
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Marco Pagni and C. Victor Jongeneel
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- 2001
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17. Searching the Expressed Sequence Tag (EST) Databases: Panning for Genes.
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C. Victor Jongeneel
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- 2000
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18. Rapid and selective surveillance of Arabidopsis thaliana genome annotations with Centrifuge.
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Florence Armand, Philipp Bucher, C. Victor Jongeneel, and Edward E. Farmer
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- 2005
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19. trome, trEST and trGEN: databases of predicted protein sequences.
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Peter Sperisen, Christian Iseli, Marco Pagni, Brian J. Stevenson, Philipp Bucher, and C. Victor Jongeneel
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- 2004
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20. EuroDia: a beta-cell gene expression resource.
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Robin Liechti, Gábor Csárdi, Sven Bergmann, Frédéric Schütz, Thierry Sengstag, Sylvia F. Boj, Joan-Marc Servitja, Jorge Ferrer, Leentje Van Lommel, Frans Schuit, Sonia Klinger, Bernard Thorens, Najib Naamane, Decio L. Eizirik, Lorella Marselli, Marco Bugliani, Piero Marchetti, Stephanie Lucas, Cecilia Holm, C. Victor Jongeneel, and Ioannis Xenarios
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- 2010
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21. The need for a human gene index.
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C. Victor Jongeneel
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- 2000
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22. Organizing and running bioinformatics hackathons within Africa: The H3ABioNet cloud computing experience [version 2; peer review: 2 approved, 1 approved with reservations]
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Azza E. Ahmed, Phelelani T. Mpangase, Sumir Panji, Shakuntala Baichoo, Yassine Souilmi, Faisal M. Fadlelmola, Mustafa Alghali, Shaun Aron, Hocine Bendou, Eugene De Beste, Mamana Mbiyavanga, Oussema Souiai, Long Yi, Jennie Zermeno, Don Armstrong, Brian D. O'Connor, Liudmila Sergeevna Mainzer, Michael R. Crusoe, Ayton Meintjes, Peter Van Heusden, Gerrit Botha, Fourie Joubert, C. Victor Jongeneel, Scott Hazelhurst, and Nicola Mulder
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lcsh:R ,lcsh:Medicine ,lcsh:Q ,lcsh:Science - Abstract
The need for portable and reproducible genomics analysis pipelines is growing globally as well as in Africa, especially with the growth of collaborative projects like the Human Health and Heredity in Africa Consortium (H3Africa). The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for portable, reproducible pipelines adapted to heterogeneous computing environments, and for the nurturing of technical expertise in workflow languages and containerization technologies. Building on the network’s Standard Operating Procedures (SOPs) for common genomic analyses, H3ABioNet arranged its first Cloud Computing and Reproducible Workflows Hackathon in 2016, with the purpose of translating those SOPs into analysis pipelines able to run on heterogeneous computing environments and meeting the needs of H3Africa research projects. This paper describes the preparations for this hackathon and reflects upon the lessons learned about its impact on building the technical and scientific expertise of African researchers. The workflows developed were made publicly available in GitHub repositories and deposited as container images on Quay.io.
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- 2019
23. Swiss EMBnet node web server.
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Laurent Falquet, Lorenza Bordoli, Vassilios Ioannidis, Marco Pagni, and C. Victor Jongeneel
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- 2003
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24. KnowEnG: a knowledge engine for genomics
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Jiawei Han, Saurabh Sinha, Richard M. Weinshilboum, Jun S. Song, and C. Victor Jongeneel
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business.industry ,Computer science ,Knowledge Bases ,media_common.quotation_subject ,Big data ,Datasets as Topic ,Health Informatics ,Genomics ,Data science ,United States ,National Institutes of Health (U.S.) ,Knowledge base ,Excellence ,Network mining ,Scalability ,Humans ,Center (algebra and category theory) ,business ,Brief Communications on Big Data ,media_common - Abstract
We describe here the vision, motivations, and research plans of the National Institutes of Health Center for Excellence in Big Data Computing at the University of Illinois, Urbana-Champaign. The Center is organized around the construction of “Knowledge Engine for Genomics” (KnowEnG), an E-science framework for genomics where biomedical scientists will have access to powerful methods of data mining, network mining, and machine learning to extract knowledge out of genomics data. The scientist will come to KnowEnG with their own data sets in the form of spreadsheets and ask KnowEnG to analyze those data sets in the light of a massive knowledge base of community data sets called the “Knowledge Network” that will be at the heart of the system. The Center is undertaking discovery projects aimed at testing the utility of KnowEnG for transforming big data to knowledge. These projects span a broad range of biological enquiry, from pharmacogenomics (in collaboration with Mayo Clinic) to transcriptomics of human behavior.
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- 2015
25. Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network
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Shaun Aron, Mamana Mbiyavanga, Lerato E Magosi, Efejiro Ashano, Christopher J. Fields, C. Victor Jongeneel, Danny Mugutso, Phelelani T. Mpangase, Sumir Panji, Venesa Pillay, Seun Adeyemi, Adaobi Okafor, Oluwadamila Falola, Hocine Bendou, Ananyo Choudhury, Olaleye Oladipo, Ezekiel Adebiyi, Radhika S. Khetani, Ovokeraye Achinike-Oduaran, Bola Akanle, Richard J. Munthali, Suresh Maslamoney, Ayton Meintjes, Gloria Rendon, Nicola Mulder, Trust Odia, Andrew Ndhlovu, Ravikiran Donthu, Itunuoluwa Isewon, Liesl M. Hendry, Emile R. Chimusa, Jenny Drnevich, Judit Kumuthini, Magambo Phillip Kimuda, Scott Hazelhurst, Liudmila Sergeevna Mainzer, Marion O. Adebiyi, Victoria Nembaware, Dhriti Sengupta, and Gerrit Botha
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0301 basic medicine ,Service (systems architecture) ,Computer science ,Data management ,Social Sciences ,Bioinformatics ,Database and Informatics Methods ,South Africa ,Sociology ,Databases, Genetic ,Medicine and Health Sciences ,Public and Occupational Health ,Biology (General) ,Ecology ,Health services research ,Genomics ,Research Assessment ,Sports Science ,3. Good health ,Test (assessment) ,Professions ,Computational Theory and Mathematics ,Modeling and Simulation ,Workshops ,Health Services Research ,QH301-705.5 ,Process (engineering) ,Developing country ,Black People ,Nigeria ,Research and Analysis Methods ,Education ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Genome-Wide Association Studies ,Genetics ,Humans ,Sports and Exercise Medicine ,Molecular Biology ,Exercise ,Developing Countries ,Ecology, Evolution, Behavior and Systematics ,business.industry ,Computational genomics ,Biology and Life Sciences ,Computational Biology ,Human Genetics ,Physical Activity ,Genome Analysis ,Data science ,Health Care ,030104 developmental biology ,Physical Fitness ,People and Places ,Scientists ,Database Management Systems ,Population Groupings ,business - Abstract
The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so., Author summary Many programs have been developed to boost the technical and computational skills of scientists working in low to medium income countries (LMIC), who often struggle to remain competitive with their peers in more developed parts of the world. Typically, these programs rely on intensive workshops where students acquire and exercise these skills under the supervision of experienced trainers. However, when trainees return to their home institutions, even after extensive exposure to state of the art techniques, they often find it difficult to put the skills they have acquired into practice and to establish themselves as fully independent practitioners. We have attempted to build a framework through which teams of scientists in African research groups can demonstrate that they have acquired the necessary skills to analyze different types of genomic datasets. Three teams of scientists who have successfully submitted to this assessment exercise report their positive experiences. Many potential participants have so far declined the opportunity, and we discuss the reasons for their reluctance as well as possible ways to facilitate their engagement and provide them with incentives. We argue that assessments such as this could be part of any program aiming to develop technical skills in scientists wishing to support genomic research programs.
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- 2017
26. Organizing and running bioinformatics hackathons within Africa: The H3ABioNet cloud computing experience
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Michael R. Crusoe, Liudmila Sergeevna Mainzer, Eugene de Beste, Ayton Meintjes, Gerrit Botha, Azza Ahmed, Nicola Mulder, Fourie Joubert, Shaun Aron, Don Armstrong, Sumir Panji, Shakuntala Baichoo, Hocine Bendou, Scott Hazelhurst, C. Victor Jongeneel, Peter van Heusden, Faisal M. Fadlelmola, Mamana Mbiyavanga, Phelelani T. Mpangase, Oussema Souiai, Brian O'Connor, Yassine Souilmi, Long Yi, Mustafa Alghali, and Jennie Zermeno
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0301 basic medicine ,Bioinformatics ,workflow ,business.industry ,capacity building ,Applied Mathematics ,pipeline ,Capacity building ,Symmetric multiprocessor system ,Cloud computing ,Articles ,Method Article ,Pipeline (software) ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Workflow ,Open research ,reproducible ,hackathon ,Container (abstract data type) ,Applied research ,business ,030217 neurology & neurosurgery - Abstract
The need for portable and reproducible genomics analysis pipelines is growing globally as well as in Africa, especially with the growth of collaborative projects like the Human Health and Heredity in Africa Consortium (H3Africa). The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for portable, reproducible pipelines adapted to heterogeneous computing environments, and for the nurturing of technical expertise in workflow languages and containerization technologies. Building on the network’s Standard Operating Procedures (SOPs) for common genomic analyses, H3ABioNet arranged its first Cloud Computing and Reproducible Workflows Hackathon in 2016, with the purpose of translating those SOPs into analysis pipelines able to run on heterogeneous computing environments and meeting the needs of H3Africa research projects. This paper describes the preparations for this hackathon and reflects upon the lessons learned about its impact on building the technical and scientific expertise of African researchers. The workflows developed were made publicly available in GitHub repositories and deposited as container images on Quay.io.
- Published
- 2019
27. Efficient and Scalable Workflows for Genomic Analyses
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C. Victor Jongeneel, Subho S. Banerjee, Zbigniew Kalbarczyk, Ravishankar K. Iyer, Liudmila Sergeevna Mainzer, Arjun P. Athreya, and Wen-mei W. Hwu
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0301 basic medicine ,Philosophy of design ,business.industry ,Computer science ,Distributed computing ,Volume (computing) ,Genomics ,Cloud computing ,Modular design ,computer.software_genre ,03 medical and health sciences ,030104 developmental biology ,Software ,Workflow ,Scalability ,Data mining ,business ,computer - Abstract
Recent growth in the volume of DNA sequence data and associated computational costs of extracting meaningful information warrants the need for efficient computational systems at-scale. In this work, we propose the Illinois Genomics Execution Environment (IGen), a framework for efficient and scalable genome analyses. The design philosophy of IGen is based on algorithmic analysis and extensive measurements on compute- and data-intensive genomic analyses workflows (such as variant discovery and genotyping analysis) executed on high-performance and cloud computing infrastructures. IGen leverages the advantages of existing designs and proposes new software improvements to overcome the ine ciencies we observe in our measurements. Based on these composite improvements, we demonstrate that IGen is able to accelerate the alignment from 13.1 hours to 10.8 hours (1.2x) and the variant from 10.1 hours to 1.25 hours (8x) calling on a single node, and its modular design scales e ciently in a parallel computing environment.
- Published
- 2016
28. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma
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Daniel Robyr, C. Victor Jongeneel, Keith Harshman, Armand Valsesia, Sergey Nikolaev, Olesya Bukach, Olivier Michielin, Katja Muehlethaler, Stylianos E. Antonarakis, Thanos D. Halazonetis, Corinne Gehrig, Ioannis Xenarios, Michel Guipponi, Jacques S. Beckmann, Daniel E. Speiser, Donata Rimoldi, Vincent Zoete, Christian Iseli, and Brian Stevenson
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Exome/genetics ,Skin Neoplasms ,DNA Repair ,Somatic cell ,MAP Kinase Kinase 2 ,MAP Kinase Kinase 1 ,medicine.disease_cause ,Germline ,Cohort Studies ,0302 clinical medicine ,Mitogen-Activated Protein Kinase 1/genetics ,Receptors, LDL/genetics ,Missense mutation ,ddc:576.5 ,Exome ,Melanoma ,Exome sequencing ,Mitogen-Activated Protein Kinase 1 ,Genetics ,0303 health sciences ,Mutation ,Cadherins ,030220 oncology & carcinogenesis ,Proto-Oncogene Proteins B-raf ,Ultraviolet Rays ,DNA repair ,Molecular Sequence Data ,Biology ,Tumor Suppressor Proteins/genetics ,MAP Kinase Kinase 2/antagonists & inhibitors/genetics ,Melanoma/genetics ,03 medical and health sciences ,DNA Repair/genetics ,ddc:570 ,Skin Neoplasms/genetics ,Cell Line, Tumor ,MAP Kinase Kinase 1/antagonists & inhibitors/genetics ,Proto-Oncogene Proteins B-raf/genetics ,Ultraviolet Rays/adverse effects ,medicine ,Humans ,030304 developmental biology ,Desmocollins ,COLD-PCR ,Base Sequence ,Cadherins/genetics ,Tumor Suppressor Proteins ,medicine.disease ,Receptors, LDL ,Cancer research - Abstract
We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1.
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- 2011
29. Genome-wide analysis of cancer/testis gene expression
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Yao-Tseng Chen, Piero Carninci, Oliver Hofmann, Yoshihide Hayashizaki, Ramon Chua, Winston Hide, Andrew J. G. Simpson, Tzeela Cohen, Christopher G. Maher, C. Victor Jongeneel, Otavia L. Caballero, Ulf Schaefer, Lloyd J. Old, Minna Lehvaslaiho, Brian Stevenson, Sumir Panji, and Adele Kruger
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Male ,Candidate gene ,In silico ,A Kinase Anchor Proteins ,Biology ,GPI-Linked Proteins ,Genome ,Testicular Neoplasms ,Cell Line, Tumor ,Testis ,Chromosomes, Human ,Humans ,Gene ,X chromosome ,Homeodomain Proteins ,Genetics ,Chromosomes, Human, X ,Expressed sequence tag ,Multidisciplinary ,Genome, Human ,Gene Expression Profiling ,Computational Biology ,Membrane Proteins ,Genomics ,Biological Sciences ,Gene expression profiling ,Human genome - Abstract
Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genome-wide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted ( 39 ), testis/brain-restricted ( 14 ), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testis-restricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets.
- Published
- 2008
30. Identification of a new cancer/testis gene family, CT47 , among expressed multicopy genes on the human X chromosome
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Andrew J. G. Simpson, Lloyd J. Old, C. Victor Jongeneel, Charis A. Venditti, Christian Iseli, and Yao-Tseng Chen
- Subjects
Genetics ,Cancer Research ,Chromosome ,Cancer ,Biology ,medicine.disease ,Molecular biology ,Gene cluster ,Gene expression ,Homologous chromosome ,medicine ,Gene family ,Gene ,X chromosome - Abstract
Cancer/testis (CT) genes are normally expressed in germ cells only, yet are reactivated and expressed in some tumors. Of the approximately 40 CT genes or gene families identified to date, 20 are on the X chromosome and are present as multigene families, many with highly conserved members. This indicates that novel CT gene families may be identified by detecting duplicated expressed genes on chromosome X. By searching for transcript clusters that map to multiple locations on the chromosome, followed by in silico analysis of their gene expression profiles, we identified five novel gene families with testis-specific expression and >98% sequence identity among family members. The expression of these genes in normal tissues and various tumor cell lines and specimens was evaluated by qualitative and quantitative RT-PCR, and a novel CT gene family with at least 13 copies was identified on Xq24, designated as CT47. mRNA expression of CT47 was found mainly in the testes, with weak expression in the placenta. Brain tissue was the only positive somatic tissue tested, with an estimated CT47 transcript level 0.09% of that found in testis. Among the tumor specimens tested, CT47 expression was found in approximately 15% of lung cancer and esophageal cancer specimens, but not in colorectal cancer or breast cancer. The putative CT47 protein consists of 288 amino acid residues, with a C-terminus rich in alanine and glutamic acid. The only species other than human in which a gene homologous to CT47 has been detected is the chimpanzee, with the predicted protein showing approximately 80% identity in its carboxy terminal region.
- Published
- 2005
31. Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes
- Author
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Leila Parand, Lakshman Subrahmanyan, Corinne Gehrig, Maryline Gagnebin, Robert Lyle, Jacques Rougemont, Homa Attar, C. Victor Jongeneel, Stylianos E. Antonarakis, Samuel Deutsch, and Emmanouil T. Dermitzakis
- Subjects
Transcription, Genetic ,Chromosomes, Human, Pair 21 ,Quantitative Trait Loci ,Down-Regulation ,Quantitative trait locus ,Biology ,Genetic linkage ,Gene expression ,Genetics ,Humans ,Lymphocytes ,International HapMap Project ,Molecular Biology ,Gene ,Genetics (clinical) ,ddc:616 ,Down-Regulation/ genetics ,Gene Expression Profiling ,Chromosome Mapping ,Chromosome ,General Medicine ,Lymphocytes/metabolism ,Chromosomes, Human, Pair 21/ genetics ,Gene Expression Regulation ,Expression quantitative trait loci ,Chromosome 21 - Abstract
Inter-individual differences in gene expression are likely to account for an important fraction of phenotypic differences, including susceptibility to common disorders. Recent studies have shown extensive variation in gene expression levels in humans and other organisms, and that a fraction of this variation is under genetic control. We investigated the patterns of gene expression variation in a 25 Mb region of human chromosome 21, which has been associated with many Down syndrome (DS) phenotypes. Taqman real-time PCR was used to measure expression variation of 41 genes in lymphoblastoid cells of 40 unrelated individuals. For 25 genes found to be differentially expressed, additional analysis was performed in 10 CEPH families to determine heritabilities and map loci harboring regulatory variation. Seventy-six percent of the differentially expressed genes had significant heritabilities, and genomewide linkage analysis led to the identification of significant eQTLs for nine genes. Most eQTLs were in trans, with the best result (P=7.46 x 10(-8)) obtained for TMEM1 on chromosome 12q24.33. A cis-eQTL identified for CCT8 was validated by performing an association study in 60 individuals from the HapMap project. SNP rs965951 located within CCT8 was found to be significantly associated with its expression levels (P=2.5 x 10(-5)) confirming cis-regulatory variation. The results of our study provide a representative view of expression variation of chromosome 21 genes, identify loci involved in their regulation and suggest that genes, for which expression differences are significantly larger than 1.5-fold in control samples, are unlikely to be involved in DS-phenotypes present in all affected individuals.
- Published
- 2005
32. An atlas of human gene expression from massively parallel signature sequencing (MPSS)
- Author
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Irina Khrebtukova, C. Victor Jongeneel, Mauro Delorenzi, Andrew J. G. Simpson, Robert L. Strausberg, Thomas J. Vasicek, Daixing Zhou, Christian Iseli, Christian D. Haudenschild, Brian Stevenson, and Dmitry Kuznetsov
- Subjects
Expressed Sequence Tags ,Genetics ,Expressed sequence tag ,Gene Expression Profiling ,Gene Expression ,Computational biology ,Biology ,Resources ,Massively parallel signature sequencing ,Transcriptome ,Gene expression profiling ,Genetic Techniques ,Organ Specificity ,Gene expression ,Humans ,Human genome ,RNA, Messenger ,Gene ,Algorithms ,Genetics (clinical) - Abstract
We have used massively parallel signature sequencing (MPSS) to sample the transcriptomes of 32 normal human tissues to an unprecedented depth, thus documenting the patterns of expression of almost 20,000 genes with high sensitivity and specificity. The data confirm the widely held belief that differences in gene expression between cell and tissue types are largely determined by transcripts derived from a limited number of tissue-specific genes, rather than by combinations of more promiscuously expressed genes. Expression of a little more than half of all known human genes seems to account for both the common requirements and the specific functions of the tissues sampled. A classification of tissues based on patterns of gene expression largely reproduces classifications based on anatomical and biochemical properties. The unbiased sampling of the human transcriptome achieved by MPSS supports the idea that most human genes have been mapped, if not functionally characterized. This data set should prove useful for the identification of tissue-specific genes, for the study of global changes induced by pathological conditions, and for the definition of a minimal set of genes necessary for basic cell maintenance. The data are available on the Web at http://mpss.licr.org and http://sgb.lynxgen.com.
- Published
- 2005
33. MyHits: a new interactive resource for protein annotation and domain identification
- Author
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Laurent Falquet, C. Victor Jongeneel, Monique Zahn-Zabal, Vassilios Ioannidis, Marco Pagni, and Lorenzo Cerutti
- Subjects
InterPro ,Web server ,Biology ,PROSITE ,computer.software_genre ,Bioinformatics ,User-Computer Interface ,Annotation ,Upload ,Protein Annotation ,Sequence Analysis, Protein ,Computer Graphics ,Genetics ,Databases, Protein ,Internet ,Information retrieval ,business.industry ,Articles ,Protein Structure, Tertiary ,Systems Integration ,The Internet ,User interface ,business ,Sequence Alignment ,computer ,Software - Abstract
The MyHits web server (http://myhits.isb-sib.ch) is a new integrated service dedicated to the annotation of protein sequences and to the analysis of their domains and signatures. Guest users can use the system anonymously, with full access to (i) standard bioinformatics programs (e.g. PSI-BLAST, ClustalW, T-Coffee, Jalview); (ii) a large number of protein sequence databases, including standard (Swiss-Prot, TrEMBL) and locally developed databases (splice variants); (iii) databases of protein motifs (Prosite, Interpro); (iv) a precomputed list of matches (‘hits’) between the sequence and motif databases. All databases are updated on a weekly basis and the hit list is kept up to date incrementally. The MyHits server also includes a new collection of tools to generate graphical representations of pairwise and multiple sequence alignments including their annotated features. Free registration enables users to upload their own sequences and motifs to private databases. These are then made available through the same web interface and the same set of analytical tools. Registered users can manage their own sequences and annotations using only web tools and freeze their data in their private database for publication purposes.
- Published
- 2004
34. High Frequency of Alternative Splicing of Human Genes Participating in the HIV-1 Life Cycle
- Author
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Brian Stevenson, Manuel Favre, Amalio Telenti, Christophe Butticaz, and C. Victor Jongeneel
- Subjects
Chromosomal Proteins, Non-Histone ,Molecular Sequence Data ,Protein domain ,Promyelocytic Leukemia Protein ,Biology ,Gene Frequency ,Viral life cycle ,GTP-Binding Proteins ,Humans ,TSG101 ,Pharmacology (medical) ,splice ,Gene ,Genetics ,Expressed sequence tag ,Base Sequence ,Endosomal Sorting Complexes Required for Transport ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Suppressor Proteins ,Alternative splicing ,Computational Biology ,Nuclear Proteins ,SMARCB1 Protein ,beta-Transducin Repeat-Containing Proteins ,Neoplasm Proteins ,DNA-Binding Proteins ,Alternative Splicing ,Infectious Diseases ,HIV-1 ,Human genome ,Cyclophilin A ,Transcription Factors - Abstract
Alternative splicing may generate splice forms with different biologic roles or missing protein domains implicated in the interaction with HIV-1. To address this issue, 6 human genes were investigated-tumor suppressor gene 101 (TSG101), beta-transducin repeats containing protein (betaTrCP), peptidyl-proly cis-trans isomerase, cyclophilin A (PPIA), integrase interactor 1 protein (INI1), Nef-associated factor 1 (NAF1), and promyelacytic leukemia (PML)-involved in the viral life cycle and HIV-1 pathogenesis. All 6 genes presented alternative splicing, and a combined bioinformatic and reverse transcription polymerase chain reaction (RT-PCR) analysis identified 27 new variants for a total of 53 splice forms (an average of 9 variants per gene). The predicted frequency of the various splice forms based on expressed sequence tags (EST) analysis corresponded to the semiquantitative findings on RT-PCR analysis for the cell culture systems and for native CD4 cells investigated. Interindividual variation in the frequencies of various splice forms in CD4 T cells from blood donors was observed for INI1. Cell type-specific variation of splice pattern was observed for NAF1. Eight splice forms lacked or modified motifs implicated in the interaction with HIV-1, underscoring the potential interest of assessing alternative splicing when investigating viral cell biology and pathogenesis.
- Published
- 2003
35. Identification of 9 novel transcripts and two RGSL genes within the hereditary prostate cancer region (HPC1) at 1q25
- Author
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Otavia L. Caballero, Ana Paula M Silva, Anamaria A. Camargo, Elisson C. Osório, Brian Stevenson, Anna Christina M. Salim, Christian Iseli, Adriana Bulgarelli, Jorge Estefano Santana de Souza, C. Victor Jongeneel, Andrew J. G. Simpson, and Sandro J. de Souza
- Subjects
Male ,Candidate gene ,DNA, Complementary ,Transcription, Genetic ,Molecular Sequence Data ,Biology ,law.invention ,Prostate cancer ,law ,Prostate ,Tumor Cells, Cultured ,Genetics ,medicine ,Humans ,Gene ,Polymerase chain reaction ,Genomic organization ,Expressed Sequence Tags ,Expressed sequence tag ,Chromosome Mapping ,Prostatic Neoplasms ,Proteins ,Chromosome ,Sequence Analysis, DNA ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Chromosomes, Human, Pair 1 ,Databases, Nucleic Acid ,RGS Proteins ,Microsatellite Repeats - Abstract
We applied a systematic bioinformatics approach, followed by careful manual inspection and experimental validation to identify additional expressed sequences located at the Hereditary Prostate Cancer Region (HPC1) between D1S2818 and D1S1642 on chromosome 1q25. All transcripts already described for the 1q25 region were identified and we were able to define 11 additional expressed sequences within this region (three full-length cDNA clone sequences and eight ESTs), increasing the total number of gene count in this region by 38%. Five out of the 11 expressed sequences identified were shown to be expressed in prostate tissue and thus represent novel disease gene candidates for the HPC1 region. Here, we report a detailed characterization of these five novel disease gene candidates, their expression pattern in various tissues, their genomic organization and functional annotation. Two candidates (RGSL1 and RGSL2) correspond to novel members of the RGS family, which is involved in the regulation of G-protein signaling. RGSL1 and RGLS2 expression was detected by real-time polymerase chain reaction in normal prostate tissue, but could not be detected in prostate tumor cell lines, suggesting they might have a role in prostate cancer.
- Published
- 2003
36. Numerous potentially functional but non-genic conserved sequences on human chromosome 21
- Author
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Stylianos E. Antonarakis, C. Victor Jongeneel, Samuel Deutsch, Volker Flegel, Philipp Bucher, Nathalie Scamuffa, Brian Stevenson, Emmanouil T. Dermitzakis, Catherine Ucla, Robert Lyle, and Alexandre Reymond
- Subjects
RNA, Untranslated/genetics ,Genomics ,Computational biology ,Biology ,Synteny ,Genome ,Conserved sequence ,Conserved non-coding sequence ,Mice/ genetics ,Animals ,Humans ,Genes/genetics ,Oligonucleotide Array Sequence Analysis ,Transcription, Genetic/genetics ,ddc:616 ,Comparative genomics ,Genetics ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,Conserved Sequence/ genetics ,Computational Biology ,Pseudogenes/genetics ,Genome project ,Regulatory Sequences, Nucleic Acid/genetics ,Chromosomes, Human, Pair 21/ genetics ,Rabbits ,Chromosome 21 ,Sequence Alignment - Abstract
The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.
- Published
- 2002
37. Long-Range Heterogeneity at the 3′ Ends of Human mRNAs
- Author
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Andrew J. G. Simpson, Brian Stevenson, Anamaria A. Camargo, Sandro J. de Souza, Philipp Bucher, Helena B. Samaia, Robert L. Strausberg, C. Victor Jongeneel, Christian Iseli, and Kenneth H. Buetow
- Subjects
Regulation of gene expression ,Genetics ,Expressed sequence tag ,Letter ,Polyadenylation ,Computational biology ,Biology ,ENCODE ,Genome ,Gene expression profiling ,Genetic Heterogeneity ,Complementary DNA ,Humans ,Human genome ,3' Flanking Region ,RNA, Messenger ,Genetics (clinical) - Abstract
The publication of a draft of the human genome and of large collections of transcribed sequences has made it possible to study the complex relationship between the transcriptome and the genome. In the work presented here, we have focused on mapping mRNA 3′ ends onto the genome by use of the raw data generated by the expressed sequence tag (EST) sequencing projects. We find that at least half of the human genes encode multiple transcripts whose polyadenylation is driven by multiple signals. The corresponding transcript 3′ ends are spread over distances in the kilobase range. This finding has profound implications for our understanding of gene expression regulation and of the diversity of human transcripts, for the design of cDNA microarray probes, and for the interpretation of gene expression profiling experiments.[The following individuals kindly provided reagents, samples or unpublished information as indicated in the paper: G. Riggins, C. Ruegg, J.-B. Demoulin, P. Olsson, F. Funari, P. Schneider, L.F. Reis, and J.-C. Renauld]
- Published
- 2002
38. Impaired Fetal Thymocyte Development After Efficient Adenovirus-Mediated Inhibition of NF-κB Activation
- Author
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Talitha R. Bakker, Toufic Renno, and C. Victor Jongeneel
- Subjects
Immunology ,Immunology and Allergy - Abstract
We introduce a new experimental system combining adenovirus-mediated gene transfer and fetal thymic organ culture (FTOC). This system allowed us to efficiently express in developing thymocytes a mutant form of the NF-κB inhibitor IκBα (mut-IκB) and to study the maturation defects occurring when NF-κB activation is inhibited during fetal development. Fetal thymocytes infected with adenovirus containing mut-IκB were found to develop normally until the CD44−CD25+, CD4−CD8− double-negative stage, while production of more mature double-positive and single-positive populations was strongly decreased. Proliferation, as measured by the percentage of cells in cycle appeared normal, as did rearrangement and expression of the TCR β-chain. However, apoptosis was much higher in FTOC infected with adenovirus containing mut-IκB than in FTOC infected with a control virus. Taken together, these results suggest that NF-κB plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development.
- Published
- 1999
39. Role of Glutathione in Macrophage Activation: Effect of Cellular Glutathione Depletion on Nitrite Production and Leishmanicidal Activity
- Author
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Yolande Buchmüller-Rouiller, Pascal Schneider, Josiane Smith, C. Victor Jongeneel, Sally Betz Corradin, Jacques Mauël, and Adriana Ransijn
- Subjects
Male ,Immunology ,Biology ,Nitric Oxide ,Mice ,chemistry.chemical_compound ,Methionine Sulfoximine ,Sulfhydryl reagent ,Animals ,Secretion ,Buthionine sulfoximine ,RNA, Messenger ,Viability assay ,Enzyme Inhibitors ,Nitrite ,Buthionine Sulfoximine ,Leishmaniasis ,Cells, Cultured ,Nitrites ,Maleates ,Glutathione ,Macrophage Activation ,Cytosol ,Biochemistry ,chemistry ,Mice, Inbred CBA ,Female ,Amino Acid Oxidoreductases ,Nitric Oxide Synthase ,Intracellular - Abstract
We have examined the effects of two agents depleting the intracellular pool of glutathione (GSH) on macrophage activation induced by IFN-gamma + LPS, as measured by nitrite production and leishmanicidal activity. Diethylmaleate (DEM), which depletes intracellular GSH by conjugation via a reaction catalyzed by the GSH-S-transferase, strongly inhibited nitrite secretion and leishmanicidal activity when added before or at the time of addition of IFN-gamma + LPS; this inhibition was progressively lost when addition of DEM was delayed up to 10 hr. A close correlation was observed between levels of intracellular soluble GSH during activation and nitrite secretion. Inhibition was partially reversed by the addition of glutathione ethyl ester (GSH-Et). Buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, also inhibited macrophage activation, although to a lesser extent than DEM despite a more pronounced soluble GSH depletion. This inhibition was completely reversed by the addition of GSH-Et. DEM and BSO did not alter cell viability or PMA-triggered O2- production by activated macrophages, suggesting that the inhibitory effects observed on nitrite secretion and leishmanicidal activity were not related to a general impairment of macrophage function. DEM and BSO treatment reduced iNOS specific activity and iNOS protein in cytosolic extracts. DEM also decreased iNOS mRNA expression while BSO had no effect. Although commonly used as a GSH-depleting agent, DEM may have additional effects because it can also act as a sulhydryl reagent; BSO, on the other hand, which depletes GSH by enzymatic inhibition, has no effect on protein-bound GSH. Our results suggest that both soluble and protein-bound GSH may be important for the induction of NO synthase in IFN-gamma + LPS-activated macrophages.
- Published
- 1995
40. Nickel and skin irritants up-regulate tumor necrosis factor-α mRNA in keratinocytes by different but potentially synergistic mechanisms
- Author
-
Kai M. Müller, Conrad Hauser, C. Victor Jongeneel, Steen Lisby, and Jean-Hilaire Saurat
- Subjects
Keratinocytes ,Transcription, Genetic ,Immunology ,Piperazines ,Cell Line ,Chloramphenicol acetyltransferase ,Mice ,Nickel ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,medicine ,Animals ,Immunology and Allergy ,Dimethyl Sulfoxide ,RNA, Messenger ,Allergic contact dermatitis ,Protein Kinase C ,Protein kinase C ,Mice, Inbred BALB C ,Messenger RNA ,Tumor Necrosis Factor-alpha ,Chemistry ,Sodium Dodecyl Sulfate ,Drug Synergism ,General Medicine ,Isoquinolines ,medicine.disease ,Molecular biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Cell culture ,Dermatitis, Allergic Contact ,Irritants ,Irritant contact dermatitis ,Tetradecanoylphorbol Acetate ,Tumor necrosis factor alpha ,Keratinocyte - Abstract
A critical role of tumor necrosis factor (TNF)-alpha in irritant contact dermatitis and in the challenge phase of allergic contact dermatitis has recently been demonstrated in vivo. As in situ hybridization studies have indicated that keratinocytes were the cellular source of TNF-alpha in these reactions, we studied the mechanisms of TNF-alpha mRNA induction in keratinocytes by agents that induce contact dermatitis. Murine la-/CD3- epidermal cells were stimulated with phorbol myristate acetate (PMA), dimethylsulfoxide (DMSO), sodium dodecyl sulfate (SDS) and NiSO4, all of which up-regulated epidermal cell TNF-alpha mRNA production. In contrast, trinitrobenzenesulfonic acid and trinitrochlorobenzene did not significantly up-regulate TNF-alpha mRNA. These results were confirmed with murine keratinocyte cell lines. In keratinocytes transfected with a chloramphenicol acetyltransferase construct containing the -1059 to +138 base pair TNF-alpha promoter, increased promoter activity was observed upon stimulation with PMA and DMSO. In addition, PMA stimulation did not affect the stability of TNF-alpha mRNA. The PMA- but also the DMSO- and SDS- induced up-regulation of TNF-alpha mRNA was abolished by an inhibitor of protein kinase C (PKC). In contrast, NiSO4 up-regulated TNF-alpha mRNA by a PKC-independent mechanism, did not increase TNF-alpha promoter activity, but markedly increased the stability of the TNF-alpha mRNA. Co-stimulation with PMA and NiSO4 induced a marked increase in TNF-alpha mRNA over that obtained with each agent alone. Thus, whereas PKC-dependent irritants act by up-regulating TNF-alpha promoter activity, nickel acts via post-transcriptional regulation. Our results also establish that some irritants and irritant sensitizers directly induce TNF-alpha in keratinocytes without intermediate Langerhans cell-derived signals.
- Published
- 1995
41. MyHits: improvements to an interactive resource for analyzing protein sequences
- Author
-
Jörg Hau, Laurent Falquet, Dmitri Kuznetsov, Vassilios Ioannidis, Monique Zahn-Zabal, Lorenzo Cerutti, Marco Pagni, C. Victor Jongeneel, and Olivier Martin
- Subjects
Service (systems architecture) ,Interface (Java) ,Biology ,Bioinformatics ,computer.software_genre ,Web API ,03 medical and health sciences ,User-Computer Interface ,Sequence Analysis, Protein ,Genetics ,Computer Graphics ,Databases, Protein ,030304 developmental biology ,Database engine ,0303 health sciences ,Internet ,Database ,business.industry ,030302 biochemistry & molecular biology ,Computational Biology ,Usability ,Articles ,Protein Structure, Tertiary ,Systems Integration ,The Internet ,Programming Languages ,User interface ,Web service ,business ,computer ,Sequence Alignment ,Software - Abstract
The MyHits web site (http://myhits.isb-sib.ch) is an integrated service dedicated to the analysis of protein sequences. Since its first description in 2004, both the user interface and the back end of the server were improved. A number of tools (e.g. MAFFT, Jacop, Dotlet, Jalview, ESTScan) were added or updated to improve the usability of the service. The MySQL schema and its associated API were revamped and the database engine (HitKeeper) was separated from the web interface. This paper summarizes the current status of the server, with an emphasis on the new services.
- Published
- 2007
42. Rapid evolution of cancer/testis genes on the X chromosome
- Author
-
C. Victor Jongeneel, Andrew J. R. Simpson, Christian Iseli, Winston Hide, Brian Stevenson, Sumir Panji, Monique Zahn-Zabal, and Lloyd J. Old
- Subjects
Male ,lcsh:QH426-470 ,Pan troglodytes ,lcsh:Biotechnology ,Biology ,Polymerase Chain Reaction ,Chimpanzee genome project ,Evolution, Molecular ,lcsh:TP248.13-248.65 ,Testis ,Genetics ,Animals ,Humans ,Gene ,X chromosome ,Expressed Sequence Tags ,Expressed sequence tag ,Chromosomes, Human, X ,Autosome ,Genome, Human ,Female ,Gene Expression Regulation, Neoplastic ,Genes, Neoplasm ,Immunotherapy ,Sequence Alignment ,Chromosome ,lcsh:Genetics ,Human genome ,DNA microarray ,Research Article ,Biotechnology - Abstract
Background Cancer/testis (CT) genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole. Results To shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes) genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes. Conclusion Given their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.
- Published
- 2007
43. Indexing strategies for rapid searches of short words in genome sequences
- Author
-
Philipp Bucher, C. Victor Jongeneel, Giovanna Ambrosini, and Christian Iseli
- Subjects
Sequence analysis ,Science ,Evolutionary Biology/Bioinformatics ,Computational Biology/Comparative Sequence Analysis ,Biology ,Genome ,Molecular Biology/Bioinformatics ,Set (abstract data type) ,Mice ,Animals ,Humans ,Genetics and Genomics/Genomics ,Genetics ,Sequence ,Multidisciplinary ,Information retrieval ,Search engine indexing ,Computational Biology ,Genetics and Genomics/Gene Expression ,Sequence Analysis, DNA ,Genetics and Genomics/Bioinformatics ,Molecular Biology/Transcription Initiation and Activation ,Task (computing) ,Index (publishing) ,Computational Biology/Sequence Motif Analysis ,Medicine ,Genetics and Genomics/Gene Discovery ,Molecular Biology/RNA-Protein Interactions ,User interface ,Databases, Nucleic Acid ,Software ,Research Article ,Computational Biology/Genomics - Abstract
Searching for matches between large collections of short (14–30 nucleotides) words and sequence databases comprising full genomes or transcriptomes is a common task in biological sequence analysis. We investigated the performance of simple indexing strategies for handling such tasks and developed two programs, fetchGWI and tagger, that index either the database or the query set. Either strategy outperforms megablast for searches with more than 10,000 probes. FetchGWI is shown to be a versatile tool for rapidly searching multiple genomes, whose performance is limited in most cases by the speed of access to the filesystem. We have made publicly available a Web interface for searching the human, mouse, and several other genomes and transcriptomes with oligonucleotide queries.
- Published
- 2007
44. Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data
- Author
-
Christian Iseli, Anita Grigoriadis, Alan Ashworth, Jorge S. Reis-Filho, Haukur Valgeirsson, Alan Mackay, Robert L. Strausberg, Michael J. O'Hare, Maria Leao, Brian Stevenson, A. Munro Neville, Dawn Steele, Andrew J. G. Simpson, C. Victor Jongeneel, Marjan Iravani, Parmjit S. Jat, and Kerry Fenwick
- Subjects
Cell type ,Transcription, Genetic ,Microarray ,Cells ,Oncology and Carcinogenesis ,Breast Neoplasms ,Biology ,Massively parallel signature sequencing ,Transcriptome ,Genetic ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Humans ,Oncology & Carcinogenesis ,Breast ,skin and connective tissue diseases ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Medicine(all) ,Cultured ,Tumor ,Tissue microarray ,Gene Expression Profiling ,Myoepithelial cell ,Epithelial Cells ,Breast Neoplasms/genetics ,Cell Adhesion Molecules/genetics ,Female ,Prognosis ,Tumor Markers, Biological/analysis ,Molecular biology ,Tumor Cells ,Gene expression profiling ,Gene chip analysis ,Cancer research ,Transcription ,Cell Adhesion Molecules ,Biomarkers ,Research Article - Abstract
INTRODUCTION: Diverse microarray and sequencing technologies have been widely used to characterise the molecular changes in malignant epithelial cells in breast cancers. Such gene expression studies to identify markers and targets in tumour cells are, however, compromised by the cellular heterogeneity of solid breast tumours and by the lack of appropriate counterparts representing normal breast epithelial cells. METHODS: Malignant neoplastic epithelial cells from primary breast cancers and luminal and myoepithelial cells isolated from normal human breast tissue were isolated by immunomagnetic separation methods. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using massively parallel signature sequencing (MPSS) and four different genome wide microarray platforms. Functional related transcripts of the differential tumour epithelial transcriptome were used for gene set enrichment analysis to identify enrichment of luminal and myoepithelial type genes. Clinical pathological validation of a small number of genes was performed on tissue microarrays. RESULTS: MPSS identified 6,553 differentially expressed genes between the pool of normal luminal cells and that of primary tumours substantially enriched for epithelial cells, of which 98% were represented and 60% were confirmed by microarray profiling. Significant expression level changes between these two samples detected only by microarray technology were shown by 4,149 transcripts, resulting in a combined differential tumour epithelial transcriptome of 8,051 genes. Microarray gene signatures identified a comprehensive list of 907 and 955 transcripts whose expression differed between luminal epithelial cells and myoepithelial cells, respectively. Functional annotation and gene set enrichment analysis highlighted a group of genes related to skeletal development that were associated with the myoepithelial/basal cells and upregulated in the tumour sample. One of the most highly overexpressed genes in this category, that encoding periostin, was analysed immunohistochemically on breast cancer tissue microarrays and its expression in neoplastic cells correlated with poor outcome in a cohort of poor prognosis estrogen receptor-positive tumours. CONCLUSION: Using highly enriched cell populations in combination with multiplatform gene expression profiling studies, a comprehensive analysis of molecular changes between the normal and malignant breast tissue was established. This study provides a basis for the identification of novel and potentially important targets for diagnosis, prognosis and therapy in breast cancer.
- Published
- 2006
45. Identification of a new cancer/testis gene family, CT47, among expressed multicopy genes on the human X chromosome
- Author
-
Yao-Tseng, Chen, Christian, Iseli, Charis A, Venditti, Lloyd J, Old, Andrew J G, Simpson, and C Victor, Jongeneel
- Subjects
Expressed Sequence Tags ,Male ,Chromosomes, Human, X ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Gene Dosage ,Proteins ,Antigens, Neoplasm ,Cell Line, Tumor ,Multigene Family ,Neoplasms ,Testis ,Humans ,Female ,Genes, Neoplasm - Abstract
Cancer/testis (CT) genes are normally expressed in germ cells only, yet are reactivated and expressed in some tumors. Of the approximately 40 CT genes or gene families identified to date, 20 are on the X chromosome and are present as multigene families, many with highly conserved members. This indicates that novel CT gene families may be identified by detecting duplicated expressed genes on chromosome X. By searching for transcript clusters that map to multiple locations on the chromosome, followed by in silico analysis of their gene expression profiles, we identified five novel gene families with testis-specific expression and98% sequence identity among family members. The expression of these genes in normal tissues and various tumor cell lines and specimens was evaluated by qualitative and quantitative RT-PCR, and a novel CT gene family with at least 13 copies was identified on Xq24, designated as CT47. mRNA expression of CT47 was found mainly in the testes, with weak expression in the placenta. Brain tissue was the only positive somatic tissue tested, with an estimated CT47 transcript level 0.09% of that found in testis. Among the tumor specimens tested, CT47 expression was found in approximately 15% of lung cancer and esophageal cancer specimens, but not in colorectal cancer or breast cancer. The putative CT47 protein consists of 288 amino acid residues, with a C-terminus rich in alanine and glutamic acid. The only species other than human in which a gene homologous to CT47 has been detected is the chimpanzee, with the predicted protein showing approximately 80% identity in its carboxy terminal region.
- Published
- 2005
46. Bioinformatics: Technical Aspects
- Author
-
C. Victor Jongeneel
- Subjects
Software ,business.industry ,Computer science ,Software engineering ,business - Published
- 2005
47. Identification of cancer/testis-antigen genes by massively parallel signature sequencing
- Author
-
Andrew J. G. Simpson, Brian Stevenson, Christian Iseli, Tom Vasicek, Lloyd J. Old, Matthew J. Scanlan, Charis A. Venditti, Robert L. Strausberg, C. Victor Jongeneel, Ali O. Gure, Ramon Chua, Yao-Tseng Chen, and Grégory Theiler
- Subjects
Male ,DNA, Complementary ,Molecular Sequence Data ,Biology ,Massively parallel signature sequencing ,Antigens, Neoplasm ,Complementary DNA ,Cell Line, Tumor ,Testis ,medicine ,Gene family ,Humans ,RNA, Messenger ,Gene ,DNA Primers ,Expressed Sequence Tags ,Expressed sequence tag ,Chromosomes, Human, X ,Multidisciplinary ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Sequence Analysis, RNA ,Gene Expression Profiling ,Cancer ,Computational Biology ,Biological Sciences ,medicine.disease ,Molecular biology ,Gene expression profiling ,Multigene Family ,Cancer/testis antigens ,Databases, Nucleic Acid - Abstract
Massively parallel signature sequencing (MPSS) generates millions of short sequence tags corresponding to transcripts from a single RNA preparation. Most MPSS tags can be unambiguously assigned to genes, thereby generating a comprehensive expression profile of the tissue of origin. From the comparison of MPSS data from 32 normal human tissues, we identified 1,056 genes that are predominantly expressed in the testis. Further evaluation by using MPSS tags from cancer cell lines and EST data from a wide variety of tumors identified 202 of these genes as candidates for encoding cancer/testis (CT) antigens. Of these genes, the expression in normal tissues was assessed by RT-PCR in a subset of 166 intron-containing genes, and those with confirmed testis-predominant expression were further evaluated for their expression in 21 cancer cell lines. Thus, 20 CT or CT-like genes were identified, with several exhibiting expression in five or more of the cancer cell lines examined. One of these genes is a member of a CT gene family that we designated as CT45. The CT45 family comprises six highly similar (>98% cDNA identity) genes that are clustered in tandem within a 125-kb region on Xq26.3. CT45 was found to be frequently expressed in both cancer cell lines and lung cancer specimens. Thus, MPSS analysis has resulted in a significant extension of our knowledge of CT antigens, leading to the discovery of a distinctive X-linked CT-antigen gene family.
- Published
- 2005
48. Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein
- Author
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Yao-Tseng, Chen, Charis A, Venditti, Gregory, Theiler, Brian J, Stevenson, Christian, Iseli, Ali O, Gure, C Victor, Jongeneel, Lloyd J, Old, and Andrew J G, Simpson
- Subjects
Male ,Meiosis ,Base Sequence ,Antigens, Neoplasm ,Reverse Transcriptase Polymerase Chain Reaction ,Molecular Sequence Data ,Testis ,Animals ,Humans ,Amino Acid Sequence - Abstract
Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.
- Published
- 2005
49. Rapid and selective surveillance of Arabidopsis thaliana genome annotations with Centrifuge
- Author
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Edward E. Farmer, C. Victor Jongeneel, Florence Armand, and Philipp Bucher
- Subjects
Statistics and Probability ,InterPro ,Arabidopsis ,Word search ,Biochemistry ,Genome ,User-Computer Interface ,Computer Graphics ,Molecular Biology ,Gene ,Caenorhabditis elegans ,Genetics ,biology ,Arabidopsis Proteins ,Gene Expression Profiling ,Chromosome Mapping ,food and beverages ,Gene Annotation ,biology.organism_classification ,Computer Science Applications ,Computational Mathematics ,Computational Theory and Mathematics ,Proteome ,Arabidopsis/genetics ,Arabidopsis/metabolism ,Arabidopsis Proteins/genetics ,Arabidopsis Proteins/metabolism ,Chromosome Mapping/methods ,Gene Expression Profiling/methods ,Software - Abstract
Summary: Centrifuge is a user-friendly system to simultaneously access Arabidopsis gene annotations and intra- and inter-organism sequence comparison data. The tool allows rapid retrieval of user-selected data for each annotated Arabidopsis gene providing, in any combination, data on the following features: predicted protein properties such as mass, pI, cellular location and transmembrane domains; SWISS-PROT annotations; Interpro domains; Gene Ontology records; verified transcription; BLAST matches to the proteomes of A.thaliana, Oryza sativa (rice), Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens. The tool lends itself particularly well to the rapid analysis of contigs or of tens or hundreds of genes identified by high-throughput gene expression experiments. In these cases, a summary table of principal predicted protein features for all genes is given followed by more detailed reports for each individual gene. Centrifuge can also be used for single gene analysis or in a word search mode. Availability: http://centrifuge.unil.ch/ Contact: edward.farmer@unil.ch
- Published
- 2005
50. Identification of the gonad-specific anion transporter SLCO6A1 as a cancer/testis (CT) antigen expressed in human lung cancer
- Author
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Sang-Yull, Lee, Barbara, Williamson, Otavia L, Caballero, Yao-Tseng, Chen, Matthew J, Scanlan, Gerd, Ritter, C Victor, Jongeneel, Andrew J G, Simpson, and Lloyd J, Old
- Subjects
Male ,Lung Neoplasms ,Antigens, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Anion Transport Proteins ,Testis ,Humans ,Organic Anion Transporters ,DNA, Neoplasm ,RNA, Messenger ,Gene Library - Abstract
Serological analysis of recombinant cDNA expression libraries (SEREX) has led to the identification of many of the antigens recognized by the immune system of cancer patients, which are collectively referred to as the cancer immunome. We used SEREX to screen a testicular cDNA expression library with sera obtained from non-small cell lung cancer patients and isolated cDNA clones for 82 antigens. These included a total of 31 antigens previously identified by SEREX, and 51 that did not match entries in the Cancer Immunome Database and were considered newly identified antigens. Overall, the antigens comprised 62 known proteins and 20 uncharacterized gene products. Six antigens (NY-TLU-6, -37, -39, -57, -70, -75) were identified as putative cell surface proteins that are potential targets for monoclonal antibody-based immunotherapy. Of these, the gonad-specific anion transport protein SLCO6A1 (NY-TLU-57) was shown to be tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis, and weakly in spleen, brain, fetal brain, and placenta. In addition, NY-TLU-57 mRNA was found in lung tumor samples (5/10) and lung cancer cell lines (6/11), as well as bladder (5/12) and esophageal (5/12) tumor samples. These data suggest that SLCO6A1 is a putative cancer/testis (CT) cell surface antigen of potential utility as a target for antibody-based therapy for a variety of tumor types. The analysis also permits us to estimate the eventual size of the SEREX-defined cancer immunome at around 4000 genes. This emphasizes the importance of continued SEREX screening to define the cancer immunome.
- Published
- 2004
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