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2.
Nat Genet ; 52(2): 231-240, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31932696

RESUMO

Pancreatic adenocarcinoma presents as a spectrum of a highly aggressive disease in patients. The basis of this disease heterogeneity has proved difficult to resolve due to poor tumor cellularity and extensive genomic instability. To address this, a dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic tumors. Transcriptome analysis demonstrated that molecular subtypes are a product of a gene expression continuum driven by a mixture of intratumoral subpopulations, which was confirmed by single-cell analysis. Integrated whole-genome analysis uncovered that molecular subtypes are linked to specific copy number aberrations in genes such as mutant KRAS and GATA6. By mapping tumor genetic histories, tetraploidization emerged as a key mutational process behind these events. Taken together, these data support the premise that the constellation of genomic aberrations in the tumor gives rise to the molecular subtype, and that disease heterogeneity is due to ongoing genomic instability during progression.

4.
Clin Exp Gastroenterol ; 12: 219-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190949

RESUMO

Purpose: The incidence of esophageal adenocarcinoma (EAC) has increased by 700% in Western countries over the last 30 years. Although clinical guidelines call for endoscopic surveillance for EAC among high-risk populations, fewer than 5% of new EAC patients are under surveillance at the time of diagnosis. We studied the accuracy of combined cytopathology and MUC2 immunohistochemistry (IHC) for screening of Intestinal Metaplasia (IM), dysplasia and EAC, using specimens collected from the EsophaCap swallowable encapsulated cytology sponge from Canada and United States. Patients and methods: By comparing the EsophaCap cytological diagnosis with concurrent endoscopic biopsies performed on the same patients in 28 cases, we first built up the cytology diagnostic categories and criteria. Based on these criteria, 136 cases were evaluated by both cytology and MUC2 IHC with blinded to patient biopsy diagnosis. Results: We first set up categories and criteria for cytological diagnosis of EscophaCap samples. Based on these, we divided our evaluated cytological samples into two groups: non-IM group and IM or dysplasia or adenocarcinoma group. Using the biopsy as our gold standard to screen IM, dysplasia and EAC by combined cytology and MUC2 IHC, the sensitivity and specificity were 68% and 91%, respectively, which is in the range of clinically useful cytological screening tests such as the cervical Pap smear. Conclusions: Combined EsophaCap cytology and MUC2 IHC could be a good screening test for IM and Beyond.

5.
Sci Rep ; 9(1): 3590, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837567

RESUMO

Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data.

6.
Head Neck ; 41(5): 1351-1358, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30554450

RESUMO

BACKGROUND: Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer. METHODS: Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient-specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre-treatment blood samples and longitudinally during standard follow-up. Circulating tumor DNA status during follow-up was correlated to disease recurrence. RESULTS: Samples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence. CONCLUSION: Circulating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.

7.
Mol Cancer Ther ; 17(4): 869-882, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29483207

RESUMO

A recurring historic finding in cancer drug development is encouraging antitumor effects observed in tumor-bearing mice that fail to translate into the clinic. An intriguing exception to this pattern is immune checkpoint therapy, as the sustained tumor regressions observed in subsets of cancer patients are rare in mice. Reasoning that this may be due in part to relatively low mutational loads of mouse tumors, we mutagenized transplantable mouse tumor cell lines EMT-6/P, B16F1, RENCA, CT26, and MC38 in vitro with methylnitro-nitrosoguanidine (MNNG) or ethylmethane sulfonate (EMS) and tested their responsiveness to PD-L1 blockade. Exome sequencing confirmed an increase in somatic mutations by mutagen treatment, an effect mimicked in EMT-6 variants chronically exposed in vivo to cisplatin or cyclophosphamide. Certain mutagenized variants of B16F1, EMT-6/P, CT26, and MC38 (but not RENCA) were more immunogenic than their parents, yet anti-PD-L1 sensitization developed only in some EMT-6/P and B16F1 variants. Treatment response patterns corresponded with changes in immune cell infiltration and especially increases in CD8+ T cells. Chronically cisplatin-exposed EMT-6 variants were also more responsive to anti-PD-L1 therapy. Although tumor PD-L1 expression was upregulated in in vivo chemotherapy-exposed variants, PD-L1 expression levels were not consistently associated with anti-PD-L1 treatment activity across mutagenized or chemotherapy-exposed variants. In summary, mutagenized and more immunogenic mouse tumors were not universally sensitized to PD-L1 blockade. Chemically mutagenized variants may be useful to evaluate the impact of immunologically "hot" or "cold" tumors with a high mutational load, to which certain chemotherapy agents may contribute, on immunotherapy outcomes. Mol Cancer Ther; 17(4); 869-82. ©2018 AACR.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/genética , Metanossulfonato de Etila/toxicidade , Neoplasias Mamárias Experimentais/genética , Melanoma Experimental/genética , Metilnitronitrosoguanidina/toxicidade , Mutação , Animais , Apoptose , Proliferação de Células , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/tratamento farmacológico , Melanoma Experimental/induzido quimicamente , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Tumorais Cultivadas
8.
Clin Cancer Res ; 24(6): 1344-1354, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29288237

RESUMO

Purpose: To perform real-time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection.Experimental Design: Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy for WGS and RNASeq. Laser capture microdissection was performed for all cases. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures.Results: Sixty-three patients underwent a tumor biopsy between December 2015 and June 2017. WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range, 19-52 days) from biopsy, meeting the primary feasibility endpoint. Objective responses to first-line chemotherapy were significantly better in patients with the classical PDAC RNA subtype compared with those with the basal-like subtype (P = 0.004). The best progression-free survival was observed in those with classical subtype treated with m-FOLFIRINOX. GATA6 expression in tumor measured by RNA in situ hybridization was found to be a robust surrogate biomarker for differentiating classical and basal-like PDAC subtypes. Potentially actionable genetic alterations were found in 30% of patients.Conclusions: Prospective genomic profiling of advanced PDAC is feasible, and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes. Clin Cancer Res; 24(6); 1344-54. ©2017 AACR.


Assuntos
Genômica , Neoplasias Pancreáticas/genética , Medicina de Precisão , Adulto , Idoso , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Dano ao DNA , Gerenciamento Clínico , Progressão da Doença , Feminino , Fator de Transcrição GATA6/genética , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Medicina de Precisão/métodos , Transcriptoma , Sequenciamento Completo do Exoma
9.
Nat Protoc ; 12(4): 664-682, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28253235

RESUMO

Detection of extremely rare variant alleles within a complex mixture of DNA molecules is becoming increasingly relevant in many areas of clinical and basic research, such as the detection of circulating tumor DNA in the plasma of cancer patients. Barcoding of DNA template molecules early in next-generation sequencing (NGS) library construction provides a way to identify and bioinformatically remove polymerase errors that otherwise make detection of these rare variants very difficult. Several barcoding strategies have been reported, but all require long and complex library preparation protocols. Simple, multiplexed, PCR-based barcoding of DNA for sensitive mutation detection using sequencing (SiMSen-seq) was developed to generate targeted barcoded libraries with minimal DNA input, flexible target selection and a very simple, short (∼4 h) library construction protocol. The protocol comprises a three-cycle barcoding PCR step followed directly by adaptor PCR to generate the library and then bead purification before sequencing. Thus, SiMSen-seq allows detection of variant alleles at <0.1% frequency with easy customization of library content (from 1 to 40+ PCR amplicons) and a protocol that can be implemented in any molecular biology laboratory. Here, we provide a detailed protocol for assay development and describe software to process the barcoded sequence reads.


Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Primers do DNA/genética , Limite de Detecção
10.
Nucleic Acids Res ; 44(11): e105, 2016 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-27060140

RESUMO

Detection of cell-free DNA in liquid biopsies offers great potential for use in non-invasive prenatal testing and as a cancer biomarker. Fetal and tumor DNA fractions however can be extremely low in these samples and ultra-sensitive methods are required for their detection. Here, we report an extremely simple and fast method for introduction of barcodes into DNA libraries made from 5 ng of DNA. Barcoded adapter primers are designed with an oligonucleotide hairpin structure to protect the molecular barcodes during the first rounds of polymerase chain reaction (PCR) and prevent them from participating in mis-priming events. Our approach enables high-level multiplexing and next-generation sequencing library construction with flexible library content. We show that uniform libraries of 1-, 5-, 13- and 31-plex can be generated. Utilizing the barcodes to generate consensus reads for each original DNA molecule reduces background sequencing noise and allows detection of variant alleles below 0.1% frequency in clonal cell line DNA and in cell-free plasma DNA. Thus, our approach bridges the gap between the highly sensitive but specific capabilities of digital PCR, which only allows a limited number of variants to be analyzed, with the broad target capability of next-generation sequencing which traditionally lacks the sensitivity to detect rare variants.


Assuntos
Código de Barras de DNA Taxonômico , Análise Mutacional de DNA , Reação em Cadeia da Polimerase Multiplex , Mutação , Biópsia , Linhagem Celular , Primers do DNA/química , Primers do DNA/genética , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA
11.
Breast Cancer Res ; 18(1): 16, 2016 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-26852132

RESUMO

BACKGROUND: Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. METHODS: We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. RESULTS: Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042). CONCLUSIONS: This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999.


Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Histonas/biossíntese , Adulto , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/administração & dosagem , Histonas/genética , Humanos , Irinotecano , Células MCF-7 , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
12.
BMC Bioinformatics ; 13: 206, 2012 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-22901030

RESUMO

BACKGROUND: It is now well established that nearly 20% of human cancers are caused by infectious agents, and the list of human oncogenic pathogens will grow in the future for a variety of cancer types. Whole tumor transcriptome and genome sequencing by next-generation sequencing technologies presents an unparalleled opportunity for pathogen detection and discovery in human tissues but requires development of new genome-wide bioinformatics tools. RESULTS: Here we present CaPSID (Computational Pathogen Sequence IDentification), a comprehensive bioinformatics platform for identifying, querying and visualizing both exogenous and endogenous pathogen nucleotide sequences in tumor genomes and transcriptomes. CaPSID includes a scalable, high performance database for data storage and a web application that integrates the genome browser JBrowse. CaPSID also provides useful metrics for sequence analysis of pre-aligned BAM files, such as gene and genome coverage, and is optimized to run efficiently on multiprocessor computers with low memory usage. CONCLUSIONS: To demonstrate the usefulness and efficiency of CaPSID, we carried out a comprehensive analysis of both a simulated dataset and transcriptome samples from ovarian cancer. CaPSID correctly identified all of the human and pathogen sequences in the simulated dataset, while in the ovarian dataset CaPSID's predictions were successfully validated in vitro.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Genoma Humano , Software , Transcriptoma , Algoritmos , Linhagem Celular Tumoral , Simulação por Computador , Feminino , Humanos , Internet , Vírus Oncogênicos/genética , Neoplasias Ovarianas/genética , Sensibilidade e Especificidade
13.
Cancer Discov ; 2(2): 172-189, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22585861

RESUMO

UNLABELLED: Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups and, on occasion, identify mutant genes that drive the cancer phenotype ("drivers"). More often, though, the functional significance of cancer-associated mutations is difficult to discern. Genome-wide pooled short hairpin RNA (shRNA) screens enable global identification of the genes essential for cancer cell survival and proliferation, providing a "functional genomic" map of human cancer to complement genomic studies. Using a lentiviral shRNA library targeting ~16,000 genes and a newly developed, dynamic scoring approach, we identified essential gene profiles in 72 breast, pancreatic, and ovarian cancer cell lines. Integrating our results with current and future genomic data should facilitate the systematic identification of drivers, unanticipated synthetic lethal relationships, and functional vulnerabilities of these tumor types. SIGNIFICANCE: This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types. SIGNIFICANCE: This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.


Assuntos
Neoplasias da Mama/genética , Neoplasias Ovarianas/genética , Neoplasias Pancreáticas/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Biblioteca Gênica , Humanos , Masculino , Neoplasias Ovarianas/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transcriptoma
14.
Wiley Interdiscip Rev RNA ; 3(4): 567-79, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22555938

RESUMO

New developments are being brought to the field of molecular biology with the mounting evidence that RNA transcripts not translated into protein (noncoding RNAs, ncRNAs) hold a variety of biological functions. Computational discovery of ncRNAs is one of these developments, fueled not only by the urge to characterize these sequences but also by necessity to prioritize ones with the most relevant functions for experimental verification. The heterogeneity in size and mode of activity of ncRNAs is reflected in the corresponding diversity of computational methods for their study. Sequence and structural analysis, conservation across species, and relative position to other genomic elements are being used for ncRNA detection. In addition, the recent development of techniques that allow deep sequencing of cell transcripts either globally or from isolated ncRNA-related material is leading the field toward increased use of such high-throughput data. We expect that imminent breakthroughs will include the classification of newer types of ncRNA and new insights into miRNA and piRNA biology, eventually leading toward the completion of a catalog of all human ncRNAs.


Assuntos
Biologia Computacional/métodos , Biologia Molecular/métodos , RNA não Traduzido/genética , Animais , Bactérias/genética , Humanos , Análise de Sequência de RNA , Vírus/genética
15.
Cell ; 147(6): 1324-39, 2011 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-22153076

RESUMO

Cherubism is an autosomal-dominant syndrome characterized by inflammatory destructive bony lesions resulting in symmetrical deformities of the facial bones. Cherubism is caused by mutations in Sh3bp2, the gene that encodes the adaptor protein 3BP2. Most identified mutations in 3BP2 lie within the peptide sequence RSPPDG. A mouse model of cherubism develops hyperactive bone-remodeling osteoclasts and systemic inflammation characterized by expansion of the myelomonocytic lineage. The mechanism by which cherubism mutations alter 3BP2 function has remained obscure. Here we show that Tankyrase, a member of the poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the SRC, SYK, and VAV signaling pathways.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Querubismo/metabolismo , Transdução de Sinais , Tanquirases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Querubismo/genética , Modelos Animais de Doenças , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Osteoclastos/metabolismo , Estabilidade Proteica , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-vav/metabolismo , Deleção de Sequência , Quinase Syk , Tanquirases/genética , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitinação
16.
PLoS One ; 6(6): e20561, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21698286

RESUMO

Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation.


Assuntos
Etiquetas de Sequências Expressas , MicroRNAs/química , Conformação de Ácido Nucleico , RNA não Traduzido/química , Animais , Northern Blotting , Linhagem Celular , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos
17.
BMC Res Notes ; 2: 39, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19284540

RESUMO

BACKGROUND: Currently one of the largest online repositories for human and mouse stem cell gene expression data, StemBase was first designed as a simple web-interface to DNA microarray data generated by the Canadian Stem Cell Network to facilitate the discovery of gene functions relevant to stem cell control and differentiation. FINDINGS: Since its creation, StemBase has grown in both size and scope into a system with analysis tools that examine either the whole database at once, or slices of data, based on tissue type, cell type or gene of interest. As of September 1, 2008, StemBase contains gene expression data (microarray and Serial Analysis of Gene Expression) from 210 stem cell samples in 60 different experiments. CONCLUSION: StemBase can be used to study gene expression in human and murine stem cells and is available at http://www.stembase.ca.

18.
Genome Biol ; 8(9): R193, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17875203

RESUMO

We describe a method for detecting marker genes in large heterogeneous collections of gene expression data. Markers are identified and characterized by the existence of demarcations in their expression values across the whole dataset, which suggest the presence of groupings of samples. We apply this method to DNA microarray data generated from 83 mouse stem cell related samples and describe 426 selected markers associated with differentiation to establish principles of stem cell evolution.


Assuntos
Células-Tronco Embrionárias/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Algoritmos , Animais , Diferenciação Celular , Biologia Computacional/métodos , Interpretação Estatística de Dados , Meio Ambiente , Marcadores Genéticos , Camundongos , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos , Filogenia , Células-Tronco/citologia
19.
Methods Mol Biol ; 407: 137-48, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18453254

RESUMO

StemBase is a database of gene expression data obtained from stem cells and derivatives mainly from mouse and human using DNA microarrays and Serial Analysis of Gene Expression. Here, we describe this database and indicate ways to use it for the study the expression of particular genes in stem cells or to search for genes with particular expression profiles in stem cells, which could be associated to stem cell function or used as stem cell markers.


Assuntos
Biomarcadores/análise , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Expressão Gênica/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Células-Tronco/fisiologia , Animais , Humanos , Camundongos
20.
FEBS Lett ; 579(8): 1795-801, 2005 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-15763554

RESUMO

DNA Microarrays are used to simultaneously measure the levels of thousands of mRNAs in a sample. We illustrate here that a collection of such measurements in different cell types and states is a sound source of functional predictions, provided the microarray experiments are analogous and the cell samples are appropriately diverse. We have used this approach to study stem cells, whose identity and mechanisms of control are not well understood, generating Affymetrix microarray data from more than 200 samples, including stem cells and their derivatives, from human and mouse. The data can be accessed online (StemBase; http://www.scgp.ca:8080/StemBase/).


Assuntos
Análise de Sequência com Séries de Oligonucleotídeos , Células-Tronco/fisiologia , Animais , Bases de Dados de Ácidos Nucleicos , Perfilação da Expressão Gênica , Humanos , Camundongos
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