Bibliographic record
Abstract
Alternative splicing, the process by which a single gene may code for similar but different proteins, is an important process in biology, linked to development, cellular differentiation, genetic diseases, and more. Genome-wide analysis of alternative splicing patterns and regulation has been recently made possible due to new high throughput techniques for monitoring gene expression and genomic sequencing. This thesis introduces two algorithms for alternative splicing analysis based on large microarray and genomic sequence data. The algorithms, based on generative probabilistic models that capture structure and patterns in the data, are used to study global properties of alternative splicing.\nIn the first part of the thesis, a microarray platform for monitoring alternative splicing is introduced. A spatial noise removal algorithm that removes artifacts and improves data fidelity is presented. The GenASAP algorithm (generative model for alternative splicing array platform) models the non-linear process in which targeted molecules bind to a microarray’s probes and is used to predict patterns of alternative splicing. Two versions of GenASAP have been developed. The first uses variational approximation to infer the relative amounts of the targeted molecules, while the second incorporates a more accurate noise and generative model and utilizes Markov chain Monte Carlo (MCMC) sampling.\nGenASAP, the first method to provide quantitative predictions of alternative splicing patterns on large scale data sets, is shown to generate useful and precise predictions based on independent RT-PCR validation (a slow but more accurate approach to measuring cellular expression patterns).\nIn the second part of the thesis, the results obtained by GenASAP are analysed to\nreveal jointly regulated genes. The sequences of the genes are examined for potential regulatory factors binding sites using a new motif finding algorithm designed for this purpose. The motif finding algorithm, called GenBITES (generative model for binding sites) uses a fully Bayesian generative model for sequences, and the MCMC approach used for inference in the model includes moves that can efficiently create or delete motifs, and extend or contract the width of existing motifs.\nGenBITES has been applied to several synthetic and real data sets, and is shown\nto be highly competitive at a task for which many algorithms already exist. Although\ndeveloped to analyze alternative splicing data, GenBITES outperforms most reported\nresults on a benchmark data set based on transcription data.
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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 | 0.003 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 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".