An atlas of human gene expression from massively parallel signature sequencing (MPSS)

Jongeneel, C. Victor; Delorenzi, Mauro; Iseli, Christian; Zhou, Daixing; Haudenschild, Christian; Khrebtukova, Irina; Kuznetsov, Dmitry; Stevenson, Brian J.; Strausberg, Robert L.; Simpson, Andrew J.G.; Vasicek, Thomas J.

doi:10.1101/gr.4041005

Cited by 148 publications

(171 citation statements)

References 20 publications

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“…Many of the 15,000 mRNAs observed in each sample were represented by only a few reads, likely indicative of either low-abundance cell types in the sample or transcriptional ''leakage.'' A prior study using massively parallel signature sequencing (MPSS) of mRNAs in human tissues concluded that Ϸ50% of the genes in the human genome are expressed in a tissue (21). Consistent with this, we observed Ϸ10,000 genes at a threshold of 20 reads per gene (Table 1 and Fig.…”

Section: Resultssupporting

confidence: 74%

Transcriptome sequencing of malignant pleural mesothelioma tumors

Sugarbaker

Richards²,

Gordon³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

141

116

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Cancers arise by the gradual accumulation of mutations in multiple genes. We now use shotgun pyrosequencing to characterize RNA mutations and expression levels unique to malignant pleural mesotheliomas (MPMs) and not present in control tissues. On average, 266 Mb of cDNA were sequenced from each of four MPMs, from a control pulmonary adenocarcinoma (ADCA), and from normal lung tissue. Previously observed differences in MPM RNA expression levels were confirmed. Point mutations were identified by using criteria that require the presence of the mutation in at least four reads and in both cDNA strands and the absence of the mutation from sequence databases, normal adjacent tissues, and other controls. In the four MPMs, 15 nonsynonymous mutations were discovered: 7 were point mutations, 3 were deletions, 4 were exclusively expressed as a consequence of imputed epigenetic silencing, and 1 was putatively expressed as a consequence of RNA editing. Notably, each MPM had a different mutation profile, and no mutated gene was previously implicated in MPM. Of the seven point mutations, three were observed in at least one tumor from 49 other MPM patients. The mutations were in genes that could be causally related to cancer and included XRCC6, PDZK1IP1, ACTR1A, and AVEN.DNA sequencing ͉ tumor mutations ͉ lung cancer ͉ bioinformatics ͉ loss of heterozygosity B ecause cancer arises as a consequence of multiple mutations, human cancer genomes are being sequenced to identify the mechanisms of tumorigenesis. Pilot sequencing studies include recent exon resequencing of tumors and cell lines that revealed somatic mutations in hundreds of genes not previously implicated in oncogenesis. These studies generally focused on a single class of mutations such as point mutations in coding regions of preselected candidate genes, and the results so far indicate that even within similar histological classes, tumors possess unique mutational profiles (1-3). However, there has rarely been an analysis of whether a mutated gene is actually expressed in the tumor cell nor has there been an attempt to use sequencing to identify other types of mutations such as chromosomal deletions or translocation (4, 5) or loss of heterozygosity related to epigenetic silencing (6, 7). Moreover, no unbiased deep sequencing analysis of all expressed genes in cancer tissues has been reported to date.Malignant pleural mesothelioma (MPM) is an asbestosrelated, rapidly fatal cancer. Its genetic basis is unknown but appears to involve multiple types of chromosomal abnormalities (5,(8)(9)(10)(11)(12)(13)(14). Central mechanisms underlying MPM are unclear, although MPM tumors evoke a strong inflammatory response thought to contribute to tumorigenesis (15). In addition, tumor cell survival promoted by TNF-␣ responsive antiapoptotic proteins such as Inhibitor of Apoptosis-1 (IAP-1) facilitates the resistance of MPM to most cytotoxic chemotherapeutic drugs (16). Expression profiling with microarrays has supported the general role of inflammation in MPM etiology and has provided...

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Section: Resultssupporting

confidence: 74%

Transcriptome sequencing of malignant pleural mesothelioma tumors

Sugarbaker

Richards²,

Gordon³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

141

116

View full text Add to dashboard Cite

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“…18 Results from the latest generations of genome-tiling microarrays and high-throughput sequencing indicate that there may be a considerably richer universe of non-coding RNAs of various sizes, produced from many different regions of the genome, than had been previously supposed. [19][20][21] In addition, comparisons between animals with increasingly complicated bodies have been used to suggest that the proportion of non-coding RNA to protein-coding RNA is correlated with developmental complexity. [22][23][24] MicroRNAs Mature microRNAs are single-stranded RNA molecules that are approximately 21 or 22 nucleotides long.…”

Section: Discovery Of Small Rnamentioning

confidence: 99%

Everything you wanted to know about small RNA but were afraid to ask

Boyd

2008

Laboratory Investigation

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MicroRNAs are a class of recently discovered small RNA molecules that regulate other genes in the human genome. Studies in human cells and model organisms have begun to reveal the mechanisms of microRNA activity, and the wide range of normal physiological functions they influence. Their alteration in pathologic states from cancer to cardiovascular disease is also increasingly clear. A review of current evidence for the role of these molecules in human health and disease will be helpful to pathologists and medical researchers as the fascinating story of these small regulators continues to unfold.

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“…In an attempt to resolve this and to identify new CT antigens, we have taken an in silico approach to produce a comprehensive survey of CT gene expression profiles by combining expression information from an existing corpus of Ͼ8,000 cDNA libraries (16) together with the depth and resolution provided by massively parallel signature sequencing (MPSS) expression libraries (17), cap-analysis of Gene Expression (CAGE) libraries (18), and a survey using semiquantitative reverse-transcription PCR (RT-PCR) on a panel of 22 normal tissues. As a result, we have created a coherent classification of CT genes, and new CT genes have been identified using well-informed, structured prediction and confirmation criteria.…”

mentioning

confidence: 99%

Genome-wide analysis of cancer/testis gene expression

Hofmann

Caballero

Stevenson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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300

309

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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 genomewide 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 testisrestricted 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.gene index ͉ prediction

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An atlas of human gene expression from massively parallel signature sequencing (MPSS)

Cited by 148 publications

References 20 publications

Transcriptome sequencing of malignant pleural mesothelioma tumors

Transcriptome sequencing of malignant pleural mesothelioma tumors

Everything you wanted to know about small RNA but were afraid to ask

Genome-wide analysis of cancer/testis gene expression

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