Dataset Information

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.

ABSTRACT: Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximately 23,500 genes, of which only approximately 1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.

SUBMITTER: Brentani H

PROVIDER: S-EPMC263829 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature

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The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.

Brentani Helena H Caballero Otávia L OL Camargo Anamaria A AA da Silva Aline M AM da Silva Wilson Araújo WA Dias Neto Emmanuel E Grivet Marco M Gruber Arthur A Guimaraes Pedro Edson Moreira PE Hide Winston W Iseli Christian C Jongeneel C Victor CV Kelso Janet J Nagai Maria Aparecida MA Ojopi Elida Paula Benquique EP Osorio Elisson C EC Reis Eduardo M R EM Riggins Gregory J GJ Simpson Andrew John George AJ de Souza Sandro S Stevenson Brian J BJ Strausberg Robert L RL Tajara Eloiza H EH Verjovski-Almeida Sergio S Acencio Marcio Luis ML Bengtson Mário Henrique MH Bettoni Fabiana F Bodmer Walter F WF Briones Marcelo R S MR Camargo Luiz Paulo LP Cavenee Webster W Cerutti Janete M JM Coelho Andrade Luis Eduardo LE Costa dos Santos Paulo César PC Ramos Costa Maria Cristina MC da Silva Israel Tojal IT Estécio Marcos Roberto H MR Sa Ferreira Karine K Furnari Frank B FB Faria Milton M Galante Pedro A F PA Guimaraes Gustavo S GS Holanda Adriano Jesus AJ Kimura Edna Teruko ET Leerkes Maarten R MR Lu Xin X Maciel Rui M B RM Martins Elizabeth A L EA Massirer Katlin Brauer KB Melo Analy S A AS Mestriner Carlos Alberto CA Miracca Elisabete Cristina EC Miranda Leandro Lorenco LL Nobrega Francisco G FG Oliveira Paulo S PS Paquola Apua C M AC Pandolfi José Rodrigo C JR Campos Pardini Maria Ines de Moura MI Passetti Fabio F Quackenbush John J Schnabel Beatriz B Sogayar Mari Cleide MC Souza Jorge E JE Valentini Sandro R SR Zaiats Andre C AC Amaral Elisabete Jorge EJ Arnaldi Liliane A T LA de Araújo Amelia Goes AG de Bessa Simone Aparecida SA Bicknell David C DC Ribeiro de Camaro Maria Eugenia ME Carraro Dirce Maria DM Carrer Helaine H Carvalho Alex F AF Colin Christian C Costa Fernando F Curcio Cyntia C Guerreiro da Silva Ismael Dale Cotrim ID Pereira da Silva Neusa N Dellamano Márcia M El-Dorry Hamza H Espreafico Enilza Maria EM Scattone Ferreira Ari José AJ Ayres Ferreira Cristiane C Fortes Maria Angela H Z MA Gama Angelita Habr AH Giannella-Neto Daniel D Giannella Maria Lúcia C C ML Giorgi Ricardo R RR Goldman Gustavo Henrique GH Goldman Maria Helena S MH Hackel Christine C Ho Paulo Lee PL Kimura Elza Myiuki EM Kowalski Luiz Paulo LP Krieger Jose E JE Leite Luciana C C LC Lopes Ademar A Luna Ana Mercedes S C AM Mackay Alan A Mari Suely Kazue Nagahashi SK Marques Adriana Aparecida AA Martins Waleska K WK Montagnini André A Mourão Neto Mario M Nascimento Ana Lucia T O AL Neville A Munro AM Nobrega Marina P MP O'Hare Mike J MJ Otsuka Audrey Yumi AY Ruas de Melo Anna Izabel AI Paco-Larson Maria Luisa ML Guimarães Pereira Gonçalo G Pereira da Silva Neusa N Pesquero Joao Bosco JB Pessoa Juliana Gilbert JG Rahal Paula P Rainho Claudia Aparecida CA Rodrigues Vanderlei V Rogatto Silvia Regina SR Romano Camila Malta CM Romeiro Janaina Gusmao JG Rossi Benedito Mauro BM Rusticci Monica M Guerra de Sá Renata R Sant' Anna Simone Cristina SC Sarmazo Miriam L ML Silva Teresa Cristina de Lima E TC Soares Fernando Augusto FA Sonati Maria de Fátima Mde F de Freitas Sousa Josane J Queiroz Diana D Valente Valéria V Vettore André Luiz AL Villanova Fabiola Elizabeth FE Zago Marco Antonio MA Zalcberg Heloisa H

Proceedings of the National Academy of Sciences of the United States of America 20031030 23

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximately 23,500 genes, of which only approximately 1,250 ...[more]

PMID: 14593198

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Project description:BACKGROUND: We have applied a high-throughput pyrosequencing technology for transcriptome profiling of Caenorhabditis elegans in its first larval stage. Using this approach, we have generated a large amount of data for expressed sequence tags, which provides an opportunity for the discovery of putative novel transcripts and alternative splice variants that could be developmentally specific to the first larval stage. This work also demonstrates the successful and efficient application of a next generation sequencing methodology. RESULTS: We have generated over 30 million bases of novel expressed sequence tags from first larval stage worms utilizing high-throughput sequencing technology. We have shown that approximately 14% of the newly sequenced expressed sequence tags map completely or partially to genomic regions where there are no annotated genes or splice variants and therefore, imply that these are novel genetic structures. Expressed sequence tags, which map to intergenic (around 1000) and intronic regions (around 580), may represent novel transcribed regions, such as unannotated or unrecognized small protein-coding or non-protein-coding genes or splice variants. Expressed sequence tags, which map across intron-exon boundaries (around 300), indicate possible alternative splice sites, while expressed sequence tags, which map near the ends of known transcripts (around 600), suggest extension of the coding or untranslated regions. We have also discovered that intergenic and intronic expressed sequence tags, which are well conserved across different nematode species, are likely to represent non-coding RNAs. Lastly, we have incorporated available serial analysis of gene expression data generated from first larval stage worms, in order to predict novel transcripts that might be specifically or predominantly expressed in the first larval stage. CONCLUSION: We have demonstrated the use of a high-throughput sequencing methodology to efficiently produce a snap-shot of transcriptional activities occurring in the first larval stage of C. elegans development. Such application of this new sequencing technique allows for high-throughput, genome-wide experimental verification of known and novel transcripts. This study provides a more complete C. elegans transcriptome profile and, furthermore, gives insight into the evolutionary and biological complexity of this organism.

Project description:BACKGROUND: The snake venom gland is a specialized organ, which synthesizes and secretes the complex and abundant toxin proteins. Though gene expression in the snake venom gland has been extensively studied, the focus has been on the components of the venom. As far as the molecular mechanism of toxin secretion and metabolism is concerned, we still knew a little. Therefore, a fundamental question being arisen is what genes are expressed in the snake venom glands besides many toxin components? RESULTS: To examine extensively the transcripts expressed in the venom gland of Deinagkistrodon acutus and unveil the potential of its products on cellular structure and functional aspects, we generated 8696 expressed sequence tags (ESTs) from a non-normalized cDNA library. All ESTs were clustered into 3416 clusters, of which 40.16% of total ESTs belong to recognized toxin-coding sequences; 39.85% are similar to cellular transcripts; and 20.00% have no significant similarity to any known sequences. By analyzing cellular functional transcripts, we found high expression of some venom related genes and gland-specific genes, such as calglandulin EF-hand protein gene and protein disulfide isomerase gene. The transcripts of creatine kinase and NADH dehydrogenase were also identified at high level. Moreover, abundant cellular structural proteins similar to mammalian muscle tissues were also identified. The phylogenetic analysis of two snake venom toxin families of group III metalloproteinase and serine protease in suborder Colubroidea showed an early single recruitment event in the viperids evolutionary process. CONCLUSION: Gene cataloguing and profiling of the venom gland of Deinagkistrodon acutus is an essential requisite to provide molecular reagents for functional genomic studies needed for elucidating mechanisms of action of toxins and surveying physiological events taking place in the very specialized secretory tissue. So this study provides a first global view of the genetic programs for the venom gland of Deinagkistrodon acutus described so far and an insight into molecular mechanism of toxin secreting.

Dataset Information

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.

Publications

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.

Similar Datasets

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