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Record W4416215612 · doi:10.1101/gr.280569.125

Graph-based deep reinforcement learning for haplotype assembly with Ralphi

2025· preprint· en· W4416215612 on OpenAlexaff
Enzo Battistella, Anant Maheshwari, Barış Ekim, Bonnie Berger, Victoria Popic

Bibliographic record

VenueGenome Research · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsArtificial Intelligence in Medicine (Canada)
FundersNational Institutes of HealthBroad Institute
KeywordsHaplotypeGenomeReinforcement learningSet (abstract data type)AlleleGenomicsHuman genomeFragment (logic)

Abstract

fetched live from OpenAlex

Haplotype assembly is the problem of reconstructing the combination of alleles on the maternally and paternally inherited chromosome copies. Individual haplotypes are essential to our understanding of how combinations of different variants impact phenotype. In this work, we focus on read-based haplotype assembly of individual diploid genomes, which reconstructs the two haplotypes directly from read alignments at variant loci. We introduce Ralphi, a novel deep reinforcement learning framework for haplotype assembly, which integrates the representational power of deep learning with reinforcement learning to accurately partition read fragments into their respective haplotype sets. To set the reward objective for reinforcement learning, our approach uses the classic reduction of the problem to the maximum fragment cut formulation on fragment graphs, in which nodes correspond to reads and edge weights capture the conflict or agreement of the reads at shared variant sites. We train Ralphi on a diverse data set of fragment graph topologies derived from genomes in the 1000 Genomes Project. We show that Ralphi achieves lower error rates at comparable or longer haplotype block lengths over the state of the art for short and long reads at varying coverage in standard human genome benchmarks.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.007
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.012
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.007
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.058
GPT teacher head0.372
Teacher spread0.314 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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