A QUASI-LIKELIHOOD METHOD TO DETECT DIFFERENTIALLY EXPRESSED GENES IN RNA-SEQUENCE DATA
Bibliographic record
Abstract
In recent years, the RNA-sequencing (RNA-seq) method, which measures the transcriptome by counting short sequencing reads obtained by high-throughput sequencing, is replacing the microarray technology as the major platform in gene expression studies. The large amount of discrete data in RNA-seq experiments calls for effective analysis methods. In this dissertation, a new method to detect differentially expressed genes based on quasi-likelihood theory is developed in experiments with a completely randomized design with two experimental conditions. The proposed method estimates the variance function empirically and consequently it has similar sensitivities and FDRs across distributions with different variance functions. In a simulation study, the method is shown to have similar sensitivities and FDRs across the data with three different types of variance functions compared with some other popular methods. This method is applied to a real dataset with two experimental conditions along with some competing methods. The new method is then extended to more complex designs such as an experiment with multiple experimental conditions, an experiment with block design and an experiment with factorial design. The same advantages for the new method have been found in simulation studies. This method and some competing methods are applied to three real datasets with complex designs. The new method is also applied to analyze reads per kilobase per million mapped reads (RPKM) data. In the simulation, the method is compared with the Linear Models for Microarray Data (LIMMA) originally developed for microarray analysis (Smyth, 2004) and the question of normalization is also examined. It is shown that the new method and the LIMMA method have similar performance. Further normalization is required for the proper analysis of the RPKM data and the best such normalization is the scaling method. Analyzing raw count data properly has better performance than analyzing the RPKM data. Different normalization and statistical methods are applied to a real dataset with varied gene length across samples.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".