| 1. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 2. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 3. |
- Jin, Yuesheng, et al.
(författare)
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Cytogenetic and fluorescence in situ hybridization characterization of clonal chromosomal aberrations and CCND1 amplification in esophageal carcinomas
- 2004
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 148:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic analyses of four squamous cell carcinomas (SCC) of the esophagus showed complex numerical and structural abnormalities. Chromosomal bands or regions preferentially involved were 11q13, 8q10, 21q10, 3p10similar top11, 1p11similar toq11, 5p11similar toq11, and 14p11similar toq11. For the first time, to our knowledge, recurrent aberrations were identified in esophageal SCC, including homogenous staining region (hsr), isochromosomes i(3q) and i(21q), and ring chromosome. Losses of chromosomal material dominated over gains. Recurrent imbalances included under-representation of 4p13similar topter, 5q14similar toqter, 9p22similar topter, 10p, 11p13similar topter, 12p13similar topter, 17p10similar topter, 18p11similar topter, 21p, and 22p, as well as over-representation of 1q25similar toqter, 3q, 7q, and 8q. Interestingly, hsr at different chromosomal regions occur-red in three of four cases. With the application of fluorescence in situ hybridization (FISH) and multicolor combined binary ratio labeling-FISH with specific DNA probes, it could be shown that in two cases the hsr was derived from chromosome 11 material and that the amplicon included CCND1. Our results, together with previous molecular genetic findings, indicate that CCND1 might be a prime target in 11q13 amplification, and that amplification of this gene might be crucial in the tumorigenesis of esophageal SCC. These observed chromosomal aberrations and imbalances thus provide important information for further molecular genetic investigation of esophageal SCC. (C) 2004 Elsevier Inc. All rights reserved.
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| 4. |
- Jin, Yuesheng, et al.
(författare)
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Cytogenetic and molecular genetic characterization of immortalized human ovarian surface epithelial cell lines: consistent loss of chromosome 13 and amplification of chromosome 20
- 2004
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 92:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. Methods. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. Results. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the lists were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. Conclusion. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis. (C) 2003 Elsevier Inc. All rights reserved.
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| 5. |
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| 6. |
- Zhang, H, et al.
(författare)
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Sequential cytogenetic and molecular cytogenetic characterization of an SV40T-immortalized nasopharyngeal cell line transformed by Epstein-Barr virus latent membrane protein-1 gene
- 2004
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 150:2, s. 144-152
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic and molecular cytogenetic analyses were performed on four sublines derived from a newly established, SV40T-immortalized nasopharyngeal (NP) cell line, NP69, with two of the sublines expressing LMP1, an Epstein-Barr virus-encoded gene. A total of seven cytogenetically related subclones were identified, all having highly complex karyotypes with massive numerical and structural rearrangements. Centromeric rearrangements in the form of isochromosomes and whole-ann translocations were prevalent. A cytogenetic sign of gene amplification [i.e., homogeneously staining region (HSR)] was detected at 1q25 in all metaphase cells analyzed. Multicolor combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) was used to confirm the karyotypic interpretations. Furthermore, multicolor COBRA-FISH also showed that part of the HSR contained chromosome 20 material. Extensive clonal evolution could be observed by the assessment of karyotypic variation among different subclones and individual metaphase cells. The evaluation of clonal evolution enabled the identification of the temporal order of chromosome aberrations during cell immortalization and malignant transformation. A striking karyotypic similarity was found between sublines expressing LMP1 and an NP carcinoma cell line, with loss of genetic material from chromosome arm 3p being an important recurrent observation. More interestingly, the karyotypic features of NP69 were also similar to those of many epithelial malignancies. Our observations suggest that serial transformation of NP cell lines might provide a useful in vitro model for the study of the multistep neoplastic transformation of NP cells.
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| 7. |
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| 8. |
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| 9. |
- Hu, Y. C., et al.
(författare)
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HPFBench : A High Performance Fortran benchmark suite
- 2000
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Ingår i: ACM Transactions on Mathematical Software. - : Association for Computing Machinery (ACM). - 0098-3500 .- 1557-7295. ; 26:1, s. 99-149
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Tidskriftsartikel (refereegranskat)abstract
- The High Performance Fortran (HPF) benchmark suite HPFBench is designed for evaluating the HPF language and compilers on scalable architectures. The functionality of the benchmarks covers scientific software library functions and application kernels that reflect the computational structure and communication patterns in fluid dynamic simulations, fundamental physics, and molecular studies in chemistry and biology. The benchmarks are characterized in terms of FLOP count, memory usage, communication pattern, local memory accesses, array allocation mechanism, as well as operation and communication counts per iteration. The benchmarks output performance evaluation metrics in the form of elapsed times, FLOP rates, and communication time breakdowns. We also provide a benchmark guide to aid the choice of subsets of the benchmarks for evaluating particular aspects of an HPF compiler. Furthermore, we report an evaluation of an industry-leading HPF compiler from the Portland Group Inc. using the HPFBench benchmarks on the distributed-memory IBM SP2.
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| 10. |
- Huang, YM, et al.
(författare)
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Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression
- 2001
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 7:2, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) are important antigen presenting cells (APC) and play a major role in initiating and orchestrating immune responses by priming T cells. Little is known about involvement of DC in multiple sclerosis (MS), where auto-aggressive T cells against myelin autoantigens are considered to contribute to inflammation and demyelination in the central nervous system. In this study, we compared phenotype and cytokine secretion of DC from patients with MS, other neurological diseases (OND) and healthy subjects. DC were generated from blood adherent mononuclear cells (MNC) by culture for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield and morphology of DC were similar in MS patients and controls. In both, the DC phenotype was that of immature myeloid lineage, comprising CD1a+ and CD11c+. The proportion of CD1a+ DC, being important for presentation of lipid antigens to T cells, was higher in MS patients compared to controls. The proportion of CD86+ DC, a co-stimulatory molecule that is assumed to promote Th2 differentiation, was low in MS. Low proportions of CD86+ DC were only observed in untreated MS patients but not in patients treated with IFN-b. Production of IL-10 and IL-12 p40 by DC did not differ in MS patients and controls. These findings indicate that alterations of functionally important surface molecules on DC are associated with MS.
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