Assessing the Feasibility of Learning Biomedical Phenotype Patterns Using High-Throughput Omics Profiles
Bibliographic record
Abstract
A decade after the completion of the human genome project, the rapid advancement of the high-throughput measurement technologies has made omics (genomics, epigenomics, transcriptomics, metabolomics) profiling feasible. The availability of such omics profiles has raised the hope for the development of more accurate disease models that will help improve the existing clinical strategies for disease prevention, diagnosis, prognosis, and treatment. Revealing the hidden pattern of diseases based on high-throughput omics profiles is only feasible if we choose the appropriate informatics techniques. While the basic univariate statistical analysis techniques are applicable to some extent within the reductionist paradigm of disease studies, supervised machine learning techniques are relevant in the systems biology paradigm of disease studies. This dissertation utilizes such machine learning techniques and foundations to analyze, experimentally and analytically, the feasibility of learning breast cancer and ancestral origins based on a genome wide scan of single nucleotide polymorphisms. In the former task, using a dataset from Alberta with 696 samples (348 breast cancer cases and 348 controls) over 900K features, we achieved 59.55% leave-one-out cross validation accuracy in breast cancer susceptibility prediction, after examining a wide range of supervised learning methods. In the latter task, using the international HapMap project phase II and III dataset with hundreds of samples with different continental and subcontinental ancestral origins over 900K or 1450K features, we developed a novel learning method, ETHNOPRED, that achieved over 90% 10 fold cross validation accuracies in various continental, and subcontinental population identification problems. Our sample complexity analysis (in the probably approximately correct learning framework) suggests that the ancestral origin prediction task is a case of realizable learning with many irrelevant features and so requires only a relatively small number of instances, while the breast cancer prediction task appears to be a case of unrealizable learning with relevant hidden features and hidden subclasses, explaining why it requires a large number of instances to be learned effectively, which we suspect is why the results here were not as good.
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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 | 0.012 | 0.025 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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".