Dataset Information

Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.

ABSTRACT: Babelomics is a response to the growing necessity of integrating and analyzing different types of genomic data in an environment that allows an easy functional interpretation of the results. Babelomics includes a complete suite of methods for the analysis of gene expression data that include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale genotyping assays (case controls and TDTs, and allows population stratification analysis and correction). All these genomic data analysis facilities are integrated and connected to multiple options for the functional interpretation of the experiments. Different methods of functional enrichment or gene set enrichment can be used to understand the functional basis of the experiment analyzed. Many sources of biological information, which include functional (GO, KEGG, Biocarta, Reactome, etc.), regulatory (Transfac, Jaspar, ORegAnno, miRNAs, etc.), text-mining or protein-protein interaction modules can be used for this purpose. Finally a tool for the de novo functional annotation of sequences has been included in the system. This provides support for the functional analysis of non-model species. Mirrors of Babelomics or command line execution of their individual components are now possible. Babelomics is available at http://www.babelomics.org.

SUBMITTER: Medina I

PROVIDER: S-EPMC2896184 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.

Medina Ignacio I Carbonell José J Pulido Luis L Madeira Sara C SC Goetz Stefan S Conesa Ana A Tárraga Joaquín J Pascual-Montano Alberto A Nogales-Cadenas Ruben R Santoyo Javier J García Francisco F Marbà Martina M Montaner David D Dopazo Joaquín J

Nucleic acids research 20100516 Web Server issue

Babelomics is a response to the growing necessity of integrating and analyzing different types of genomic data in an environment that allows an easy functional interpretation of the results. Babelomics includes a complete suite of methods for the analysis of gene expression data that include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale genotyping ass ...[more]

PMID: 20478823

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Project description:BackgroundIn the past decade, RNA sequencing and mass spectrometry based quantitative approaches are being used commonly to identify the differentially expressed biomarkers in different biological conditions. Data generated from these approaches come in different sizes (e.g., count matrix, normalized list of differentially expressed biomarkers, etc.) and shapes (e.g., sequences, spectral data, etc.). The list of differentially expressed biomarkers is used for functional interpretation and retrieve biological meaning, however, it requires moderate computational skills. Thus, researchers with no programming expertise find difficulty in data interpretation. Several bioinformatics tools are available to analyze such data; however, they are less flexible for performing the multiple steps of visualization and functional interpretation.ImplementationWe developed an easy-to-use Shiny based web application (named as OMnalysis) that provides users with a single platform to analyze and visualize the differentially expressed data. The OMnalysis accepts the data in tabular form from edgeR, DESeq2, MaxQuant Perseus, R packages, and other similar software, which typically contains the list of differentially expressed genes or proteins, log of the fold change, log of the count per million, the P value, q-value, etc. The key features of the OMnalysis are multiple image type visualization and their dimension customization options, seven multiple hypothesis testing correction methods to get more significant gene ontology, network topology-based pathway analysis, and multiple databases support (KEGG, Reactome, PANTHER, biocarta, NCI-Nature Pathway Interaction Database PharmGKB and STRINGdb) for extensive pathway enrichment analysis. OMnalysis also fetches the literature information from PubMed to provide supportive evidence to the biomarkers identified in the analysis. In a nutshell, we present the OMnalysis as a well-organized user interface, supported by peer-reviewed R packages with updated databases for quick interpretation of the differential transcriptomics and proteomics data to biological meaning.AvailabilityThe OMnalysis codes are entirely written in R language and freely available at https://github.com/Punit201016/OMnalysis. OMnalysis can also be accessed from - http://lbmi.uvlf.sk/omnalysis.html. OMnalysis is hosted on a Shiny server at https://omnalysis.shinyapps.io/OMnalysis/. The minimum system requirements are: 4 gigabytes of RAM, i3 processor (or equivalent). It is compatible with any operating system (windows, Linux or Mac). The OMnalysis is heavily tested on Chrome web browsers; thus, Chrome is the preferred browser. OMnalysis works on Firefox and Safari.

Project description:Spaceflight presents a unique environment with complex stressors, including microgravity and radiation, that can influence plant physiology at molecular levels. Combining transcriptomics and proteomics approaches, this research gives insights into the coordination of transcriptome and proteome in Arabidopsis' molecular and physiological responses to Spaceflight environmental stress. Arabidopsis seedlings were germinated and grown in microgravity (µg) aboard the International Space Station (ISS) in NASA Biological Research in Canisters - Light Emitting Diode (BRIC LED) hardware, with the ground control established on Earth. At 10 days old, seedlings were frozen in RNA-later and returned to Earth. RNA-seq transcriptomics and TMT-labeled LC-MS/MS proteomic analysis of cellular fractionates from the plant tissues suggest the alteration of the photosynthetic machinery (PSII and PSI) in spaceflight, with the plant shifting photosystem core-regulatory proteins in an organ-specific manner to adapt to the microgravity environment. An overview of the ribosome, spliceosome, and proteasome activities in spaceflight revealed a significant abundance of transcripts and proteins involved in protease binding, nuclease activities, and mRNA binding in spaceflight, while those involved in tRNA binding, exoribonuclease activity, and RNA helicase activity were less abundant in spaceflight. CELLULOSE SYNTHASES (CESA1, CESA3, CESA5, CESA7) and CELLULOSE-LIKE PROTEINS (CSLE1, CSLG3), involved in cellulose deposition and TUBULIN COFACTOR B (TFCB) had reduced abundance in spaceflight. This contrasts with the increased expression of UDP-ARABINOPYRANOSE MUTASEs, involved in the biosynthesis of cell wall non-cellulosic polysaccharides, in spaceflight. Both transcripts and proteome suggested an altered polar auxin redistribution, lipid, and ionic intracellular transportation in spaceflight. Analyses also suggest an increased metabolic energy requirement for plants in Space than on Earth, hence, the activation of several shunt metabolic pathways. This study provides novel insights, based on integrated RNA and protein data, on how plants adapt to the spaceflight environment and it is a step further at achieving sustainable crop production in Space.

Project description:BackgroundPancreatic cancer is a deadly disease with a five-year survival of less than 5%. A better understanding of the underlying biology may suggest novel therapeutic targets. Recent surveys of the pancreatic cancer genome have uncovered numerous new alterations; yet systematic functional characterization of candidate cancer genes has lagged behind. To address this challenge, here we have devised a highly-parallel RNA interference-based functional screen to evaluate many genomically-nominated candidate pancreatic cancer genes simultaneously.ResultsFor 185 candidate pancreatic cancer genes, selected from recurrently altered genomic loci, we performed a pooled shRNA library screen of cell growth/viability across 10 different cell lines. Knockdown-associated effects on cell growth were assessed by enrichment or depletion of shRNA hairpins, by hybridization to barcode microarrays. A novel analytical approach (COrrelated Phenotypes for On-Target Effects; COPOTE) was used to discern probable on-target knockdown, based on identifying different shRNAs targeting the same gene and displaying concordant phenotypes across cell lines. Knockdown data were integrated with genomic architecture and gene-expression profiles, and selected findings validated using individual shRNAs and/or independent siRNAs. The pooled shRNA library design delivered reproducible data. In all, COPOTE analysis identified 52 probable on-target gene-knockdowns. Knockdown of known oncogenes (KRAS, MYC, SMURF1 and CCNE1) and a tumor suppressor (CDKN2A) showed the expected contrasting effects on cell growth. In addition, the screen corroborated purported roles of PLEKHG2 and MED29 as 19q13 amplicon drivers. Most notably, the analysis also revealed novel possible oncogenic functions of nucleoporin NUP153 (ostensibly by modulating TGF? signaling) and Kruppel-like transcription factor KLF5 in pancreatic cancer.ConclusionsBy integrating physical and functional genomic data, we were able to simultaneously evaluate many candidate pancreatic cancer genes. Our findings uncover new facets of pancreatic cancer biology, with possible therapeutic implications. More broadly, our study provides a general strategy for the efficient characterization of candidate genes emerging from cancer genome studies.

Project description:ImportanceUse of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain.ObjectiveTo determine which patients derived the greatest degree of clinical benefit from NGS profiling.Design, setting, and participantsPatients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020.Main outcomes and measuresPatients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer.ResultsDuring the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses.Conclusions and relevanceThe high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.

Project description:Next-generation sequencing (NGS) approaches are commonly used to identify key regulatory networks that drive transcriptional programs. Although these technologies are frequently used in biological studies, NGS data analysis remains a challenging, time-consuming, and often irreproducible process. Therefore, there is a need for a comprehensive and flexible workflow platform that can accelerate data processing and analysis so more time can be spent on functional studies.We have developed an integrative, stand-alone workflow platform, named CIPHER, for the systematic analysis of several commonly used NGS datasets including ChIP-seq, RNA-seq, MNase-seq, DNase-seq, GRO-seq, and ATAC-seq data. CIPHER implements various open source software packages, in-house scripts, and Docker containers to analyze and process single-ended and pair-ended datasets. CIPHER's pipelines conduct extensive quality and contamination control checks, as well as comprehensive downstream analysis. A typical CIPHER workflow includes: (1) raw sequence evaluation, (2) read trimming and adapter removal, (3) read mapping and quality filtering, (4) visualization track generation, and (5) extensive quality control assessment. Furthermore, CIPHER conducts downstream analysis such as: narrow and broad peak calling, peak annotation, and motif identification for ChIP-seq, differential gene expression analysis for RNA-seq, nucleosome positioning for MNase-seq, DNase hypersensitive site mapping, site annotation and motif identification for DNase-seq, analysis of nascent transcription from Global-Run On (GRO-seq) data, and characterization of chromatin accessibility from ATAC-seq datasets. In addition, CIPHER contains an "analysis" mode that completes complex bioinformatics tasks such as enhancer discovery and provides functions to integrate various datasets together.Using public and simulated data, we demonstrate that CIPHER is an efficient and comprehensive workflow platform that can analyze several NGS datasets commonly used in genome biology studies. Additionally, CIPHER's integrative "analysis" mode allows researchers to elicit important biological information from the combined dataset analysis.

Dataset Information

Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.

Publications

Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.

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