共查询到20条相似文献,搜索用时 15 毫秒
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Genta Sawada Atsushi Niida Hidenari Hirata Hisateru Komatsu Ryutaro Uchi Teppei Shimamura Yusuke Takahashi Junji Kurashige Tae Matsumura Hiroki Ueo Yuki Takano Masami Ueda Shotaro Sakimura Yoshiaki Shinden Hidetoshi Eguchi Tomoya Sudo Keishi Sugimachi Makoto Yamasaki Fumiaki Tanaka Yuji Tachimori Yoshiaki Kajiyama Shoji Natsugoe Hiromasa Fujita Yoichi Tanaka George Calin Satoru Miyano Yuichiro Doki Masaki Mori Koshi Mimori 《PloS one》2015,10(10)
BackgroundFew driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes.MethodsWe searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.ResultsWe found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.ConclusionOur integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target. 相似文献
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Xin He Stephan J. Sanders Li Liu Silvia De Rubeis Elaine T. Lim James S. Sutcliffe Gerard D. Schellenberg Richard A. Gibbs Mark J. Daly Joseph D. Buxbaum Matthew W. State Bernie Devlin Kathryn Roeder 《PLoS genetics》2013,9(8)
De novo mutations affect risk for many diseases and disorders, especially those with early-onset. An example is autism spectrum disorders (ASD). Four recent whole-exome sequencing (WES) studies of ASD families revealed a handful of novel risk genes, based on independent de novo loss-of-function (LoF) mutations falling in the same gene, and found that de novo LoF mutations occurred at a twofold higher rate than expected by chance. However successful these studies were, they used only a small fraction of the data, excluding other types of de novo mutations and inherited rare variants. Moreover, such analyses cannot readily incorporate data from case-control studies. An important research challenge in gene discovery, therefore, is to develop statistical methods that accommodate a broader class of rare variation. We develop methods that can incorporate WES data regarding de novo mutations, inherited variants present, and variants identified within cases and controls. TADA, for Transmission And De novo Association, integrates these data by a gene-based likelihood model involving parameters for allele frequencies and gene-specific penetrances. Inference is based on a Hierarchical Bayes strategy that borrows information across all genes to infer parameters that would be difficult to estimate for individual genes. In addition to theoretical development we validated TADA using realistic simulations mimicking rare, large-effect mutations affecting risk for ASD and show it has dramatically better power than other common methods of analysis. Thus TADA''s integration of various kinds of WES data can be a highly effective means of identifying novel risk genes. Indeed, application of TADA to WES data from subjects with ASD and their families, as well as from a study of ASD subjects and controls, revealed several novel and promising ASD candidate genes with strong statistical support. 相似文献
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In the past few decades, embryonic stem cells (ESCs) were of great interest as a model system for studying early developmental processes and because of their potential therapeutic applications in regenerative medicine. However, the underlying mechanisms of ESC differentiation remain unclear, which limits our exploration of the therapeutic potential of stem cells. Fortunately, the increasing quantity and diversity of biological datasets can provide us with opportunities to explore the biological secrets. However, taking advantage of diverse biological information to facilitate the advancement of ESC research still remains a challenge. Here, we propose a scalable, efficient and flexible function prediction framework that integrates diverse biological information using a simple weighted strategy, for uncovering the genetic determinants of mouse ESC differentiation. The advantage of this approach is that it can make predictions based on dynamic information fusion, owing to the simple weighted strategy. With this approach, we identified 30 genes that had been reported to be associated with differentiation of stem cells, which we regard to be associated with differentiation or pluripotency in embryonic stem cells. We also predicted 70 genes as candidates for contributing to differentiation, which requires further confirmation. As a whole, our results showed that this strategy could be applied as a useful tool for ESC research. 相似文献
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Fenglou Mao Yanbin Yin Fengfeng Zhou Wen-Chi Chou Chan Zhou Huiling Chen Ying Xu 《Bioenergy Research》2009,2(4):209-216
We have recently developed a database, pDAWG, focused on information related to plant cell walls. Currently, pDAWG contains seven complete plant genomes, 12 complete algal genomes, along with computed information for individual proteins encoded in these genomes of the following types: (a) carbohydrate active enzyme (CAZy) family information when applicable; (b) phylogenetic trees of cell wall-related CAZy family proteins; (c) protein structure models if available; (d) physical and predicted interactions among proteins; (e) subcellular localization; (f) Pfam domain information; and (g) homology-based functional prediction. A querying system with a graphical interface allows a user to quickly compose information of different sorts about individual genes/proteins and to display the composite information in an intuitive manner, facilitating comparative analyses and knowledge discovery about cell wall genes. pDAWG can be accessed at http://csbl1.bmb.uga.edu/pDAWG/. 相似文献
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Gabriel Kremmidiotis Elizabeth Baker Joanna Crawford Helen J. Eyre Joseph Nahmias David F. Callen 《Genomics》1998,49(3):467
This report presents the chromosomal localization of cadherin genes. Cadherins are cellular adhesion molecules. Since disturbance of intracellular adhesion is important for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. A variety of solid tumors show loss of heterozygosity of the long arm of chromosome 16, which is indicative of the potential location of tumor suppressor genes. Refined and new localizations of six cadherin genes (CDH3, 5, 8, 11, 13, and 15) to the long arm of chromosome 16 are shown. CDH15 was localized to 16q24.3, in a region that exhibits loss of heterozygosity in a number of sporadic breast cancer tumors. Previous localization of CDH13 (H-cadherin) to 16q24 suggested this gene as a tumor suppressor candidate in the 16q24.3 loss of heterozygosity region; however, refined mapping presented in this report localizes CDH13 proximal to this region. A human EST homologous to the chicken cadherin-7 was partially sequenced and found to represent a new human cadherin. This cadherin mapped to chromosome 18q22–q23, a region that exhibits loss of heterozygosity in head and neck squamous cell carcinomas. CDH16 was localized to 8q22.1, a region exhibiting loss of heterozygosity in adult acute myeloid leukemia. 相似文献
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cDNA-AFLP技术是近年来广泛应用于植物基因分离与表达研究的mRNA指纹图谱技术,在分离植物特异性基因等生物技术研究中发挥了巨大作用.在植物耐盐基因鉴定方面,该技术的应用处于新兴初始阶段,但已取得了诸多成效.本文在概述植物耐盐响应机制的基础上,着重对利用cDNA-AFLP技术鉴定的植物耐盐相关基因及其相应作用机制进行了阐述,并对其在植物耐盐分子生物学研究上的应用前景进行了展望. 相似文献
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Previous attempts to identify genes in fish that respond to virus infection or interferon induction have not been particularly
productive. Since these genes are very important in developing strategies to control disease outbreaks in aquaculture, we
began a study of interferon-inducible genes in fish using suppressive subtraction hybridization to construct cDNA libraries
enriched for interferon-inducible genes. Subtraction hybridization libraries were constructed with cDNA obtained from the
kidney, spleen, and liver of Chinook salmon (Oncorhynchus tshawytscha) and staghorn sculpin (Hemilepidotus spinosus) before and after injection with poly IC, a potent interferon inducer. The ``identified' genes in both cDNA libraries corresponded
to previously identified genes of the fish complement system, the interferon-inducible proteins observed in mammalian cells,
and the Vig-1 gene, identified in fish cells after infection with fish rhabdoviruses.
Received June 19, 2001; accepted July 13, 2001 相似文献
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Xiaopei Shen Shan Li Lin Zhang Hongdong Li Guini Hong XianXiao Zhou Tingting Zheng Wenjing Zhang Chunxiang Hao Tongwei Shi Chunyang Liu Zheng Guo 《PloS one》2013,8(4)
Background
Cancer cells typically exhibit large-scale aberrant methylation of gene promoters. Some of the genes with promoter methylation alterations play “driver” roles in tumorigenesis, whereas others are only “passengers”.Results
Based on the assumption that promoter methylation alteration of a driver gene may lead to expression alternation of a set of genes associated with cancer pathways, we developed a computational framework for integrating promoter methylation and gene expression data to identify driver methylation aberrations of cancer. Applying this approach to breast cancer data, we identified many novel cancer driver genes and found that some of the identified driver genes were subtype-specific for basal-like, luminal-A and HER2+ subtypes of breast cancer.Conclusion
The proposed framework proved effective in identifying cancer driver genes from genome-wide gene methylation and expression data of cancer. These results may provide new molecular targets for potential targeted and selective epigenetic therapy. 相似文献12.
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Background
Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult.Methodology/Principal Findings
Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics.Conclusions/Significance
The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction. 相似文献16.
Geetika Sethi Harsh B. Pathak Hong Zhang Yan Zhou Margret B. Einarson Vinod Vathipadiekal Sumedha Gunewardena Michael J. Birrer Andrew K. Godwin 《PloS one》2012,7(10)
Targeted therapies have been used to combat many tumor types; however, few have effectively improved the overall survival in women with epithelial ovarian cancer, begging for a better understanding of this deadly disease and identification of essential drivers of tumorigenesis that can be targeted effectively. Therefore, we used a loss-of-function screening approach to help identify molecular vulnerabilities that may represent key points of therapeutic intervention. We employed an unbiased high-throughput lethality screen using a 24,088 siRNA library targeting over 6,000 druggable genes and studied their effects on growth and/or survival of epithelial ovarian cancer (EOC) cell lines. The top 300 “hits” affecting the viability of A1847 cells were rescreened across additional EOC cell lines and non-tumorigenic, human immortalized ovarian epithelial cell lines. Fifty-three gene candidates were found to exhibit effects in all tumorigenic cell lines tested. Extensive validation of these hits refined the list to four high quality candidates (HSPA5, NDC80, NUF2, and PTN). Mechanistic studies show that silencing of three genes leads to increased apoptosis, while HSPA5 silencing appears to alter cell growth through G1 cell cycle arrest. Furthermore, two independent gene expression studies show that NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. Overall, our functional genomics results integrated with the genomics data provide an important unbiased avenue towards the identification of prospective therapeutic targets for drug discovery, which is an urgent and unmet clinical need for ovarian cancer. 相似文献
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Rosemary W. Elliott 《Genetics》1979,91(2):295-308
Cytosol polypeptides from mouse liver have been examined using two-dimensional electrophoresis. About 250 spots were readily discernible. When cytosols from strains BALB/cBy and C57BL/6By were compared eight genetically determined differences were observed. Other strain pairs show comparable numbers of differences. These eight phenotypes were scored in seven recombinant inbred lines derived from the two parental strains, and their strain distribution patterns were compared with previously determined patterns for other genetic markers that differ between the two progenitor strains. Using this information, tentative chromosomes assignments for the genes controlling five of the variant phenotypes have been made, and two of the assignments have been confirmed using congenic resistant strains. These eight genes will be useful reference markers in future crosses designed to map new genes. 相似文献
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Neuropathological evidence from both human and experimental models of Parkinson's disease (PD) firmly supports a significant role for oxidative stress (OS) in the death of dopaminergic (DA) neurons in substantia nigra. Largely unknown are the genes underlying selective susceptibility of nigral DA neuron to OS and how they effect nigral DA cell death. The major barriers to high-throughput identification of candidate genes are the paucity of nigral DA neurons as well as the dilution effect of non-DA cells both in primary cultures and brain tissues. To overcome these barriers, we have developed a DA cell line model, SN4741, appropriate for cDNA microarray analysis. Candidate genes were selected from both the microarray analysis and the molecular implication of their pathological mechanisms (i.e., decreased mitochondrial complex I activity and proteasomal dysfunction) of PD. Subsequent secondary validation tests were devised to characterize genes including clone #45 that may underlie selective vulnerability of nigral DA neuron to OS. 相似文献
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