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1.
Nucleic Acids Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788843

RESUMO

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.

2.
Cells ; 10(8)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34440851

RESUMO

Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100-170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33+ and CD14+ myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4+ and CD8+ T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.


Assuntos
Células Dendríticas/metabolismo , Vesículas Extracelulares/metabolismo , Imunidade Adaptativa , Antígeno B7-1/metabolismo , Diferenciação Celular , Linhagem Celular , Células Dendríticas/citologia , Células Dendríticas/imunologia , Vesículas Extracelulares/transplante , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Ativação Linfocitária , Monócitos/citologia , Monócitos/metabolismo , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Linfócitos T/citologia , Linfócitos T/imunologia , Transcriptoma , Microambiente Tumoral
3.
Bioinformatics ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196689

RESUMO

MOTIVATION: Genome browsers are an essential tool in genome analysis. Modern genome browsers enable complex and interactive visualization of a wide variety of genomic data modalities. While such browsers are very powerful, they can be challenging to configure and program for bioinformaticians lacking expertise in web development. RESULTS: We have developed an R package that provides an interface to the JBrowse 2 genome browser. The package can be used to configure and customize the browser entirely with R code. The browser can be deployed from the R console, or embedded in Shiny applications or R Markdown documents. AVAILABILITY: JBrowseR is available for download from CRAN, and the source code is openly available from the Github repository at https://github.com/GMOD/JBrowseR/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics Online.

4.
Nucleic Acids Res ; 49(W1): W624-W632, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-33978761

RESUMO

Dockstore (https://dockstore.org/) is an open source platform for publishing, sharing, and finding bioinformatics tools and workflows. The platform has facilitated large-scale biomedical research collaborations by using cloud technologies to increase the Findability, Accessibility, Interoperability and Reusability (FAIR) of computational resources, thereby promoting the reproducibility of complex bioinformatics analyses. Dockstore supports a variety of source repositories, analysis frameworks, and language technologies to provide a seamless publishing platform for authors to create a centralized catalogue of scientific software. The ready-to-use packaging of hundreds of tools and workflows, combined with the implementation of interoperability standards, enables users to launch analyses across multiple environments. Dockstore is widely used, more than twenty-five high-profile organizations share analysis collections through the platform in a variety of workflow languages, including the Broad Institute's GATK best practice and COVID-19 workflows (WDL), nf-core workflows (Nextflow), the Intergalactic Workflow Commission tools (Galaxy), and workflows from Seven Bridges (CWL) to highlight just a few. Here we describe the improvements made over the last four years, including the expansion of system integrations supporting authors, the addition of collaboration features and analysis platform integrations supporting users, and other enhancements that improve the overall scientific reproducibility of Dockstore content.


Assuntos
Biologia Computacional/métodos , Disseminação de Informação , Internet , Software , Fluxo de Trabalho , Computação em Nuvem , Biologia Computacional/educação , Visualização de Dados , Humanos , National Heart, Lung, and Blood Institute (U.S.) , National Human Genome Research Institute (U.S.) , Reprodutibilidade dos Testes , Estados Unidos
5.
Nucleic Acids Res ; 49(D1): D1452-D1463, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33170273

RESUMO

Gramene (http://www.gramene.org), a knowledgebase founded on comparative functional analyses of genomic and pathway data for model plants and major crops, supports agricultural researchers worldwide. The resource is committed to open access and reproducible science based on the FAIR data principles. Since the last NAR update, we made nine releases; doubled the genome portal's content; expanded curated genes, pathways and expression sets; and implemented the Domain Informational Vocabulary Extraction (DIVE) algorithm for extracting gene function information from publications. The current release, #63 (October 2020), hosts 93 reference genomes-over 3.9 million genes in 122 947 families with orthologous and paralogous classifications. Plant Reactome portrays pathway networks using a combination of manual biocuration in rice (320 reference pathways) and orthology-based projections to 106 species. The Reactome platform facilitates comparison between reference and projected pathways, gene expression analyses and overlays of gene-gene interactions. Gramene integrates ontology-based protein structure-function annotation; information on genetic, epigenetic, expression, and phenotypic diversity; and gene functional annotations extracted from plant-focused journals using DIVE. We train plant researchers in biocuration of genes and pathways; host curated maize gene structures as tracks in the maize genome browser; and integrate curated rice genes and pathways in the Plant Reactome.


Assuntos
Bases de Dados Genéticas , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genômica/métodos , Proteínas de Plantas/genética , Plantas/genética , Produtos Agrícolas , Elementos de DNA Transponíveis , Duplicação Gênica , Ontologia Genética , Redes Reguladoras de Genes , Internet , Bases de Conhecimento , Redes e Vias Metabólicas , Anotação de Sequência Molecular , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas/classificação , Plantas/metabolismo , Poliploidia , Mapeamento de Interação de Proteínas , Software , Zea mays/genética , Zea mays/metabolismo
6.
Autophagy ; 17(6): 1543-1554, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32486891

RESUMO

The 21st century has revealed much about the fundamental cellular process of autophagy. Autophagy controls the catabolism and recycling of various cellular components both as a constitutive process and as a response to stress and foreign material invasion. There is considerable knowledge of the molecular mechanisms of autophagy, and this is still growing as new modalities emerge. There is a need to investigate autophagy mechanisms reliably, comprehensively and conveniently. Reactome is a freely available knowledgebase that consists of manually curated molecular events (reactions) organized into cellular pathways (https://reactome.org/). Pathways/reactions in Reactome are hierarchically structured, graphically presented and extensively annotated. Data analysis tools, such as pathway enrichment, expression data overlay and species comparison, are also available. For customized analysis, information can also be programmatically queried. Here, we discuss the curation and annotation of the molecular mechanisms of autophagy in Reactome. We also demonstrate the value that Reactome adds to research by reanalyzing a previously published work on genome-wide CRISPR screening of autophagy components.Abbreviations: CMA: chaperone-mediated autophagy; GO: Gene Ontology; MA: macroautophagy; MI: microautophagy; MTOR: mechanistic target of rapamycin kinase; SQSTM1: sequestosome 1.

7.
PLoS Comput Biol ; 16(8): e1007261, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810130

RESUMO

We describe JBrowse Connect, an optional expansion to the JBrowse genome browser, targeted at developers. JBrowse Connect allows live messaging, notifications for new annotation tracks, heavy-duty analyses initiated by the user from within the browser, and other dynamic features. We present example applications of JBrowse Connect that allow users 1) to specify and execute BLAST searches by either running on the same host as the webserver, with a self-contained BLAST module leveraging NCBI Blast+ commands, or via a managed Galaxy instance that can optionally run on a different host, and 2) to run the primer design service Primer3. JBrowse Connect allows users to track job progress and view results in the context of the browser. The software is available under a choice of open source licenses including LGPL and the Artistic License.


Assuntos
Bases de Dados Genéticas , Genômica/métodos , Software , Internet
10.
Nat Commun ; 11(1): 734, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024818

RESUMO

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.


Assuntos
Genômica/métodos , Mutação , Neoplasias/genética , Software , Algoritmos , Genoma Humano , Humanos , Fatores de Transcrição MEF2/genética , Taxa de Mutação , Fator 1 de Elongação de Peptídeos/genética , Receptores Acoplados a Proteínas G/genética , Sequenciamento Completo do Genoma
11.
Nat Commun ; 11(1): 728, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024849

RESUMO

In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.


Assuntos
Biologia Computacional/métodos , Aprendizado Profundo , Mutação , Neoplasias/genética , Neoplasias/patologia , Feminino , Genoma Humano , Humanos , Masculino , Metástase Neoplásica , Reprodutibilidade dos Testes , Sequenciamento Completo do Genoma
12.
Nat Genet ; 52(2): 231-240, 2020 02.
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.


Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/mortalidade , Estudos de Coortes , Feminino , Fator de Transcrição GATA6/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Smad4/genética
13.
Mol Cell ; 77(6): 1307-1321.e10, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31954095

RESUMO

A comprehensive catalog of cancer driver mutations is essential for understanding tumorigenesis and developing therapies. Exome-sequencing studies have mapped many protein-coding drivers, yet few non-coding drivers are known because genome-wide discovery is challenging. We developed a driver discovery method, ActiveDriverWGS, and analyzed 120,788 cis-regulatory modules (CRMs) across 1,844 whole tumor genomes from the ICGC-TCGA PCAWG project. We found 30 CRMs with enriched SNVs and indels (FDR < 0.05). These frequently mutated regulatory elements (FMREs) were ubiquitously active in human tissues, showed long-range chromatin interactions and mRNA abundance associations with target genes, and were enriched in motif-rewiring mutations and structural variants. Genomic deletion of one FMRE in human cells caused proliferative deficiencies and transcriptional deregulation of cancer genes CCNB1IP1, CDH1, and CDKN2B, validating observations in FMRE-mutated tumors. Pathway analysis revealed further sub-significant FMREs at cancer genes and processes, indicating an unexplored landscape of infrequent driver mutations in the non-coding genome.


Assuntos
Biomarcadores Tumorais/genética , Cromatina/metabolismo , Redes Reguladoras de Genes , Mutação , Neoplasias/genética , Neoplasias/patologia , Sequências Reguladoras de Ácido Nucleico , Proliferação de Células , Cromatina/genética , Biologia Computacional/métodos , Análise Mutacional de DNA , Genoma Humano , Células HEK293 , Humanos
14.
Nucleic Acids Res ; 48(D1): D498-D503, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31691815

RESUMO

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.


Assuntos
Bases de Dados de Compostos Químicos , Bases de Dados de Produtos Farmacêuticos , Bases de Conhecimento , Software , Genoma Humano , Humanos , Redes e Vias Metabólicas , Mapas de Interação de Proteínas , Transdução de Sinais
15.
Nucleic Acids Res ; 48(D1): D1093-D1103, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31680153

RESUMO

Plant Reactome (https://plantreactome.gramene.org) is an open-source, comparative plant pathway knowledgebase of the Gramene project. It uses Oryza sativa (rice) as a reference species for manual curation of pathways and extends pathway knowledge to another 82 plant species via gene-orthology projection using the Reactome data model and framework. It currently hosts 298 reference pathways, including metabolic and transport pathways, transcriptional networks, hormone signaling pathways, and plant developmental processes. In addition to browsing plant pathways, users can upload and analyze their omics data, such as the gene-expression data, and overlay curated or experimental gene-gene interaction data to extend pathway knowledge. The curation team actively engages researchers and students on gene and pathway curation by offering workshops and online tutorials. The Plant Reactome supports, implements and collaborates with the wider community to make data and tools related to genes, genomes, and pathways Findable, Accessible, Interoperable and Re-usable (FAIR).


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Genômica , Metabolômica , Plantas/genética , Plantas/metabolismo , Proteômica , Redes Reguladoras de Genes , Genômica/métodos , Humanos , Redes e Vias Metabólicas , Metabolômica/métodos , Proteômica/métodos , Transdução de Sinais , Navegador
16.
Nucleic Acids Res ; 48(D1): D762-D767, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31642470

RESUMO

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.


Assuntos
Caenorhabditis elegans/genética , Bases de Dados Genéticas , Genes de Helmintos , Animais , Mineração de Dados , Genômica , Internet , Interface Usuário-Computador
17.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31802127

RESUMO

Reactome is a manually curated, open-source, open-data knowledge base of biomolecular pathways. Reactome has always provided clear credit attribution for authors, curators and reviewers through fine-grained annotation of all three roles at the reaction and pathway level. These data are visible in the web interface and provided through the various data download formats. To enhance visibility and credit attribution for the work of authors, curators and reviewers, and to provide additional opportunities for Reactome community engagement, we have implemented key changes to Reactome: contributor names are now fully searchable in the web interface, and contributors can 'claim' their contributions to their ORCID profile with a few clicks. In addition, we are reaching out to domain experts to request their help in reviewing and editing Reactome pathways through a new 'Contribution' section, highlighting pathways which are awaiting community review. Database URL: https://reactome.org.


Assuntos
Curadoria de Dados , Transdução de Sinais , Interface Usuário-Computador
18.
Nat Commun ; 10(1): 5829, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863004

RESUMO

Targeting oncogenic pathways holds promise for brain tumor treatment, but inhibition of Sonic Hedgehog (SHH) signaling has failed in SHH-driven medulloblastoma. Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq and lineage tracing, we analyzed cellular diversity in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. In untreated tumors, we find expected stromal cells and tumor-derived cells showing either a spectrum of neural progenitor-differentiation states or glial and stem cell markers. Vismodegib reduces the proliferative population and increases differentiation. However, specific cell types in vismodegib-treated tumors remain proliferative, showing either persistent SHH-pathway activation or stem cell characteristics. Our data show that even in tumors with a single pathway-activating mutation, diverse mechanisms drive tumor growth. This diversity confers early resistance to targeted inhibitor therapy, demonstrating the need to target multiple pathways simultaneously.


Assuntos
Neoplasias Cerebelares/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Hedgehog/antagonistas & inibidores , Meduloblastoma/genética , Transdução de Sinais/genética , Anilidas/farmacologia , Anilidas/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Cerebelo/citologia , Cerebelo/patologia , Feminino , Mutação com Ganho de Função , Proteínas Hedgehog/genética , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/patologia , Camundongos , Camundongos Transgênicos , Terapia de Alvo Molecular/métodos , Proteína MyoD/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Piridinas/farmacologia , Piridinas/uso terapêutico , RNA-Seq , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Receptor Smoothened/genética , Fatores de Transcrição HES-1/genética
19.
Nature ; 574(7780): 712-716, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597163

RESUMO

Cancers are caused by genomic alterations known as drivers. Hundreds of drivers in coding genes are known but, to date, only a handful of noncoding drivers have been discovered-despite intensive searching1,2. Attention has recently shifted to the role of altered RNA splicing in cancer; driver mutations that lead to transcriptome-wide aberrant splicing have been identified in multiple types of cancer, although these mutations have only been found in protein-coding splicing factors such as splicing factor 3b subunit 1 (SF3B1)3-6. By contrast, cancer-related alterations in the noncoding component of the spliceosome-a series of small nuclear RNAs (snRNAs)-have barely been studied, owing to the combined challenges of characterizing noncoding cancer drivers and the repetitive nature of snRNA genes1,7,8. Here we report a highly recurrent A>C somatic mutation at the third base of U1 snRNA in several types of tumour. The primary function of U1 snRNA is to recognize the 5' splice site via base-pairing. This mutation changes the preferential A-U base-pairing between U1 snRNA and the 5' splice site to C-G base-pairing, and thus creates novel splice junctions and alters the splicing pattern of multiple genes-including known drivers of cancer. Clinically, the A>C mutation is associated with heavy alcohol use in patients with hepatocellular carcinoma, and with the aggressive subtype of chronic lymphocytic leukaemia with unmutated immunoglobulin heavy-chain variable regions. The mutation in U1 snRNA also independently confers an adverse prognosis to patients with chronic lymphocytic leukaemia. Our study demonstrates a noncoding driver in spliceosomal RNAs, reveals a mechanism of aberrant splicing in cancer and may represent a new target for treatment. Our findings also suggest that driver discovery should be extended to a wider range of genomic regions.


Assuntos
Mutação , Neoplasias/genética , RNA Nuclear Pequeno/genética , Spliceossomos/genética , Humanos , Neoplasias/patologia , Neoplasias/fisiopatologia , Sítios de Splice de RNA , Splicing de RNA , Fatores de Processamento de RNA/genética
20.
F1000Res ; 8: 908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31372215

RESUMO

The precision medicine paradigm is centered on therapies targeted to particular molecular entities that will elicit an anticipated and controlled therapeutic response. However, genetic alterations in the drug targets themselves or in genes whose products interact with the targets can affect how well a drug actually works for an individual patient. To better understand the effects of targeted therapies in patients, we need software tools capable of simultaneously visualizing patient-specific variations and drug targets in their biological context. This context can be provided using pathways, which are process-oriented representations of biological reactions, or biological networks, which represent pathway-spanning interactions among genes, proteins, and other biological entities. To address this need, we have recently enhanced the Reactome Cytoscape app, ReactomeFIViz, to assist researchers in visualizing and modeling drug and target interactions. ReactomeFIViz integrates drug-target interaction information with high quality manually curated pathways and a genome-wide human functional interaction network. Both the pathways and the functional interaction network are provided by Reactome, the most comprehensive open source biological pathway knowledgebase. We describe several examples demonstrating the application of these new features to the visualization of drugs in the contexts of pathways and networks. Complementing previous features in ReactomeFIViz, these new features enable researchers to ask focused questions about targeted therapies, such as drug sensitivity for patients with different mutation profiles, using a pathway or network perspective.


Assuntos
Sistemas de Liberação de Medicamentos , Proteínas , Software , Visualização de Dados , Humanos
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