Biological Sequence Simulation for Testing Complex Evolutionary Hypotheses: indel-Seq-Gen Version 2.0
Bibliographic record
Abstract
Sequence simulation is an important tool in validating biological hypotheses as well as testing various bioinformatics and molecular evolutionary methods. Hypothesis testing relies on the representational ability of the sequence simulation method. Simple hypotheses are testable through simulation of random, homogeneously evolving sequence sets. However, testing complex hypotheses, for example, local similarities, requires simulation of sequence evolution under heterogeneous models. To this end, we previously introduced indel-Seq-Gen version 1.0 (iSGv1.0; indel, insertion/deletion). iSGv1.0 allowed heterogeneous protein evolution and motif conservation as well as insertion and deletion constraints in subsequences. Despite these advances, for complex hypothesis testing, neither iSGv1.0 nor other currently available sequence simulation methods is sufficient. indel-Seq-Gen version 2.0 (iSGv2.0) aims at simulating evolution of highly divergent DNA sequences and protein superfamilies. iSGv2.0 improves upon iSGv1.0 through the addition of lineage-specific evolution, motif conservation using PROSITE-like regular expressions, indel tracking, subsequence-length constraints, as well as coding and noncoding DNA evolution. Furthermore, we formalize the sequence representation used for iSGv2.0 and uncover a flaw in the modeling of indels used in current state of the art methods, which biases simulation results for hypotheses involving indels. We fix this flaw in iSGv2.0 by using a novel discrete stepping procedure. Finally, we present an example simulation of the calycin-superfamily sequences and compare the performance of iSGv2.0 with iSGv1.0 and random model of sequence evolution.
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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 | 0.005 | 0.011 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.004 | 0.002 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.015 | 0.009 |
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".