Gene expression analysis identifies global gene dosage sensitivity in cancer.
paper
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- Authors
- Fehrmann, Rudolf S N; Karjalainen, Juha M; Krajewska, MaΕgorzata; Westra, Harm-Jan; Maloney, David; Simeonov, Anton; Pers, Tune H; Hirschhorn, Joel N; Jansen, Ritsert C; Schultes, Erik A; van Haagen, Herman H H B M; de Vries, Elisabeth G E; te Meerman, Gerard J; Wijmenga, Cisca; van Vugt, Marcel A T M; Franke, Lude
- Year
- 2015
- Journal
- Nature genetics
- PMID
- 25581432
- DOI
- 10.1038/ng.3173
Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying this method to 16,172 patient-derived tumor samples, we replicated many loci with aberrant copy numbers and identified recurrently disrupted genes in genomically unstable cancers.
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| The antibody-drug conjugate target landscape across a broad range of tumour types. | Moek KL et al. | β | 2017 | β |
| The Blebbishield Emergency Program Overrides Chromosomal Instability and Phagocytosis Checkpoints in Cancer Stem Cells. | Jinesh GG et al. | β | 2017 | β |
| The emerging landscape of dynamic DNA methylation in early childhood. | Xu CJ et al. | β | 2017 | β |
| The FEN1 L209P mutation interferes with long-patch base excision repair and induces cellular transformation. | Sun H et al. | β | 2017 | β |
| The functional consequences and prognostic value of dosage sensitivity in ovarian cancer. | Yan Z et al. | β | 2017 | β |
| ADAGE-Based Integration of Publicly Available <i>Pseudomonas aeruginosa</i> Gene Expression Data with Denoising Autoencoders Illuminates Microbe-Host Interactions. | Tan J et al. | β | 2016 | β |
| Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. | Ellinghaus D et al. | β | 2016 | β |
| An integrative and comparative study of pan-cancer transcriptomes reveals distinct cancer common and specific signatures. | Cao Z et al. | β | 2016 | β |
| BreCAN-DB: a repository cum browser of personalized DNA breakpoint profiles of cancer genomes. | Narang P et al. | β | 2016 | β |
| Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site. | Exell JC et al. | β | 2016 | β |
| Comprehensive analysis of schizophrenia-associated loci highlights ion channel pathways and biologically plausible candidate causal genes. | Pers TH et al. | β | 2016 | β |
| Detection and removal of spatial bias in multiwell assays. | Lachmann A et al. | β | 2016 | β |
| Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits. | Aguirre-Gamboa R et al. | β | 2016 | β |
| Dosage compensation of the sex chromosomes and autosomes. | Disteche CM | β | 2016 | β |
| Drug Repositioning through Systematic Mining of Gene Coexpression Networks in Cancer. | Ivliev AE et al. | β | 2016 | β |
| Effects of aneuploidy on gene expression: implications for cancer. | DΓΌrrbaum M et al. | β | 2016 | β |
| Expanding the Immunology Toolbox: Embracing Public-Data Reuse and Crowdsourcing. | Sparks R et al. | β | 2016 | β |
| Functional Genomics in Pharmaceutical Drug Discovery. | Adams R et al. | β | 2016 | β |
| Gene set analysis for interpreting genetic studies. | Pers TH | β | 2016 | β |
| Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. | Okbay A et al. | β | 2016 | β |
| Genetic variants in RBFOX3 are associated with sleep latency. | Amin N et al. | β | 2016 | β |
| Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. | Felix JF et al. | β | 2016 | β |
| Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. | Hyde CL et al. | β | 2016 | β |
| Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression. | Torrente A et al. | β | 2016 | β |
| Integrative analysis of human omics data using biomolecular networks. | Robinson JL et al. | β | 2016 | β |
| Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi. | Li Y et al. | β | 2016 | β |
| Iterative ensemble feature selection for multiclass classification of imbalanced microarray data. | Yang J et al. | β | 2016 | β |
| Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. | Gormley P et al. | β | 2016 | β |
| Principal components analysis and the reported low intrinsic dimensionality of gene expression microarray data. | Lenz M et al. | β | 2016 | β |
| Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs. | RicaΓ±o-Ponce I et al. | β | 2016 | β |
| Somatic Copy Number Alterations at Oncogenic Loci Show Diverse Correlations with Gene Expression. | Roszik J et al. | β | 2016 | β |
| Stable Gene Regulatory Network Modeling From Steady-State Data. | Larvie JE et al. | β | 2016 | β |
| Studying platinum sensitivity and resistance in high-grade serous ovarian cancer: Different models for different questions. | Alkema NG et al. | β | 2016 | β |
| Studying protein-protein interactions: progress, pitfalls and solutions. | Hayes S et al. | β | 2016 | β |
| Targeting DNA Flap Endonuclease 1 to Impede Breast Cancer Progression. | He L et al. | β | 2016 | β |
| The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis. | Ben-David U et al. | β | 2016 | β |
| The rules and impact of nonsense-mediated mRNA decay in human cancers. | Lindeboom RG et al. | β | 2016 | β |
| Altered Gene Expression Associated with microRNA Binding Site Polymorphisms. | VΓ΅sa U et al. | β | 2015 | β |
| An integrative systems genetics approach reveals potential causal genes and pathways related to obesity. | Kogelman LJ et al. | β | 2015 | β |
| Big data mining yields novel insights on cancer. | Jiang P et al. | β | 2015 | β |
| Biological interpretation of genome-wide association studies using predicted gene functions. | Pers TH et al. | β | 2015 | β |
| Cell Specific eQTL Analysis without Sorting Cells. | Westra HJ et al. | β | 2015 | β |
| Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types. | Lamberts LE et al. | β | 2015 | β |
| Genetic studies of body mass index yield new insights for obesity biology. | Locke AE et al. | β | 2015 | β |
| Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development. | Chan Y et al. | β | 2015 | β |
| Genome-wide association studies of human adiposity: Zooming in on synapses. | Sandholt CH et al. | β | 2015 | β |
| Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations. | Shah S et al. | β | 2015 | β |
| The impact of low-frequency and rare variants on lipid levels. | Surakka I et al. | β | 2015 | β |