Integrative analysis of layers of data in hepatocellular carcinoma reveals pathway dependencies
Bibliographic record
Abstract
BACKGROUND: The broader use of high-throughput technologies has led to improved molecular characterization of hepatocellular carcinoma (HCC). AIM: To comprehensively analyze and characterize all publicly available genomic, gene expression, methylation, miRNA and proteomic data in HCC, covering 85 studies and 3355 patient sample profiles, to identify the key dysregulated genes and pathways they affect. METHODS: We collected and curated all well-annotated and publicly available high-throughput datasets from PubMed and Gene Expression Omnibus derived from human HCC tissue. Comprehensive pathway enrichment analysis was performed using pathDIP for each data type (genomic, gene expression, methylation, miRNA and proteomic), and the overlap of pathways was assessed to elucidate pathway dependencies in HCC. RESULTS: We identified a total of 8733 abstracts retrieved by the search on PubMed on HCC for the different layers of data on human HCC samples, published until December 2016. The common key dysregulated pathways in HCC tissue across different layers of data included epidermal growth factor (EGFR) and β1-integrin pathways. Genes along these pathways were significantly and consistently dysregulated across the different types of high-throughput data and had prognostic value with respect to overall survival. Using CTD database, estradiol would best modulate and revert these genes appropriately. CONCLUSION: By analyzing and integrating all available high-throughput genomic, transcriptomic, miRNA, methylation and proteomic data from human HCC tissue, we identified EGFR, β1-integrin and axon guidance as pathway dependencies in HCC. These are master regulators of key pathways in HCC, such as the mTOR, Ras/Raf/MAPK and p53 pathways. The genes implicated in these pathways had prognostic value in HCC, with Netrin and Slit3 being novel proteins of prognostic importance to HCC. Based on this integrative analysis, EGFR, and β1-integrin are master regulators that could serve as potential therapeutic targets in HCC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.011 | 0.011 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".