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Biological Misinterpretation of Transcriptional Signatures in Tumor Samples Can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data.

Clinical cancer research : an official journal of the American Association for Cancer Research | 2022

Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling.

Pubmed ID: 35792866 RIS Download

Associated grants

  • Agency: Swiss National Science Foundation, Switzerland
    Id: 168322
  • Agency: Medical Research Council, United Kingdom
    Id: MR/V029711/1
  • Agency: Cancer Research UK, United Kingdom
    Id: A28223
  • Agency: Wellcome Trust, United Kingdom
    Id: 206314/Z/17/Z
  • Agency: Cancer Research UK, United Kingdom
    Id: A29834
  • Agency: Cancer Research UK, United Kingdom
    Id: A25142
  • Agency: Cancer Research UK, United Kingdom
    Id: C55370/A25813
  • Agency: Medical Research Council, United Kingdom
    Id: MR/M016587/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_21042
  • Agency: Cancer Research UK, United Kingdom
    Id: A26825

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This is a list of tools and resources that we have found mentioned in this publication.


Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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BioCarta Pathways (tool)

RRID:SCR_006917

BioCarta Pathways allows users to observe how genes interact in dynamic graphical models. Online maps available within this resource depict molecular relationships from areas of active research. In an open source approach, this community-fed forum constantly integrates emerging proteomic information from the scientific community. It also catalogs and summarizes important resources providing information for over 120,000 genes from multiple species. Find both classical pathways as well as current suggestions for new pathways.

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clusterProfiler (software resource)

RRID:SCR_016884

Software R package for statistical analysis and visualization of functional profiles for genes and gene clusters.

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LIMMA (software resource)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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DESeq2 (software resource)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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ggpubr (software resource)

RRID:SCR_021139

Software R package provides functions for creating and customizing ggplot2 based publication ready plots.Used for creation of ggplot2 based graphs.

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Shiny (software resource)

RRID:SCR_001626

Open source R package that provides web framework for building web applications using R. Used to create interactive web apps in native R, without needing to use HTML, CSS, or JavaScript.

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ggplot2 (data processing software)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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ComplexHeatmap (software resource)

RRID:SCR_017270

Software package to arrange multiple heatmaps and support various annotation graphics. Used to visualize associations between different sources of data sets and to reveal potential patterns.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Molecular Signatures Database (data or information resource)

RRID:SCR_016863

Collection of annotated gene sets for use with Gene Set Enrichment Analysis (GSEA) software.

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fgsea (software resource)

RRID:SCR_020938

Software R package for fast preranked gene set enrichment analysis. Allows to make more permutations and get more fine grained p-values, which allows to use accurate stantard approaches to multiple hypothesis correction.

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GSVA (data analysis software)

RRID:SCR_021058

Open source software R package for assaying variation of gene set enrichment over sample population.Used for microarray and RNA-seq data analysis. Gene set enrichment method that estimates variation of pathway activity over sample population in unsupervised manner.

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HALO (data processing software)

RRID:SCR_018350

Software image analysis platform for quantitative tissue analysis in digital pathology by Indica Labs. Used for high-throughput, quantitative tissue analysis in oncology, neuroscience, metabolism, toxicology.

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NanoString GeoMx Digital Spatial Profiler (instrument resource)

RRID:SCR_021660

Integrated commercial system comprising hardware, software and nCounter chemistry that enables simultaneous, highly multiplex spatial profiling of proteins or RNA in FFPE tissues. DSP platform quantifies abundance of protein or RNA by counting unique indexing oligonucleotides assigned to each target of interest. Used to rapidly and quantitatively assess biological implications of heterogeneity within tissue samples.

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Weighted Gene Co-expression Network Analysis (software resource)

RRID:SCR_003302

Software R package for weighted correlation network analysis. WGCNA is also available as point-and-click application. Unfortunately this application is not maintained anymore. It is known to have compatibility problems with R-2.8.x and newer, and the methods it implements are not all state of the art.

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