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Record W4313544751 · doi:10.1089/cmb.2022.0395

A Novel Information-Theory-Based Genetic Distance That Approximates Phenotypic Differences

2023· article· en· W4313544751 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Computational Biology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMachine Learning in Bioinformatics
Canadian institutionsUniversity Health Network
FundersCenters for Disease Control and PreventionNational Institutes of Health
KeywordsBiologyGeneticsPhenotypeEntropy (arrow of time)Computational biologyMajor histocompatibility complexIn silicoDistance matrixPairwise comparisonMathematicsCombinatoricsGeneStatistics

Abstract

fetched live from OpenAlex

Application of genetic distances to measure phenotypic relatedness is a challenging task, reflecting the complex relationship between genotype and phenotype. Accurate assessment of proximity among sequences with different phenotypic traits depends on how strongly the chosen distance is associated with structural and functional properties. In this study, we present a new distance measure Mutual Information and Entropy H (MIH) for categorical data such as nucleotide or amino acid sequences. MIH applies an information matrix (IM), which is calculated from the data and captures heterogeneity of individual positions as measured by Shannon entropy and coordinated substitutions among positions as measured by mutual information. In general, MIH assigns low weights to differences occurring at high entropy positions or at dependent positions. MIH distance was compared with other common distances on two experimental and two simulated data sets. MIH showed the best ability to distinguish cross-immunoreactive sequence pairs from non-cross-immunoreactive pairs of variants of the hepatitis C virus hypervariable region 1 (26,883 pairwise comparisons), and Major Histocompatibility Complex (MHC) binding peptides ( n = 181) from non-binding peptides ( n = 129). Analysis of 74 simulated RNA secondary structures also showed that the ratio between MIH distance of sequences from the same RNA structure and MIH of sequences from different structures is three orders of magnitude greater than for Hamming distances. These findings indicate that lower MIH between two sequences is associated with greater probability of the sequences to belong to the same phenotype. Examination of rule-based phenotypes generated in silico showed that (1) MIH is strongly associated with phenotypic differences, (2) IM of sequences under selection is very different from IM generated under random scenarios, and (3) IM is robust to sampling. In conclusion, MIH strongly approximates structural/functional distances and should have important applications to a wide range of biological problems, including evolution, artificial selection of biological functions and structures, and measuring phenotypic similarity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.586
Threshold uncertainty score0.393

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.012
GPT teacher head0.259
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it