ArticleCell2014
Identification of causal genetic drivers of human disease through systems-level analysis of regulatory networks.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.Scientific reports · 2015Pooled it
- An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.The Journal of investigative dermatology · 2018Trial
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- GREmLN: A Cellular Graph Structure Aware Transcriptomics Foundation Model.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the role ofWorld journal of hepatology · 2025Review
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- The Cullin3-Rbx1-KLHL9 E3 ubiquitin ligase complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation.Cell reports · 2025Article
- The Molecular Mechanisms of Imatinib Treatment on Acute Lung Injury in Septic Mice Through Proteomic Technology.Journal of immunology research · 2025Article
- Genome-wide studies define new genetic mechanisms of IgA vasculitis.medRxiv : the preprint server for health sciences · 2024Article
- Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations.NPJ systems biology and applications · 2024Article
- Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's disease.G3 (Bethesda, Md.) · 2024Article
- Transcriptional and metabolic effects of aspartate-glutamate carrier isoform 1 (AGC1) downregulation in mouse oligodendrocyte precursor cells (OPCs).Cellular & molecular biology letters · 2024Article
- Quantified pathway mutations associate epithelial-mesenchymal transition and immune escape with poor prognosis and immunotherapy resistance of head and neck squamous cell carcinoma.BMC medical genomics · 2024Article
- Molecular and cellular programs underlying the development of bovine pre-implantation embryos.Reproduction, fertility, and development · 2023Article
- Identifying genetic regulatory variants that affect transcription factor activity.Cell genomics · 2023Article
- SCING: Inference of robust, interpretable gene regulatory networks from single cell and spatial transcriptomics.iScience · 2023Article
- A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.Cancer discovery · 2023Article
- Genomic and Transcriptional Profiles ofInternational journal of molecular sciences · 2023Article
- CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway.Cell death & disease · 2023Article
- Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells.Genes · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Identification of driver mutations in human diseases is often limited by cohort size and availability of appropriate statistical models. We propose a framework for the systematic discovery of genetic alterations that are causal determinants of disease, by prioritizing genes upstream of functional disease drivers, within regulatory networks inferred de novo from experimental data. We tested this framework by identifying the genetic determinants of the mesenchymal subtype of glioblastoma. Our analysis uncovered KLHL9 deletions as upstream activators of two previously established master regulators of the subtype, C/EBPβ and C/EBPδ. Rescue of KLHL9 expression induced proteasomal degradation of C/EBP proteins, abrogated the mesenchymal signature, and reduced tumor viability in vitro and in vivo. Deletions of KLHL9 were confirmed in > 50% of mesenchymal cases in an independent cohort, thus representing the most frequent genetic determinant of the subtype. The method generalized to study other human diseases, including breast cancer and Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.