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Record W4386496033 · doi:10.1038/s41587-023-01917-2

Protein remote homology detection and structural alignment using deep learning

2023· article· en· W4386496033 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

VenueNature Biotechnology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Structure and Dynamics
Canadian institutionsYork UniversityCanadian Institute for Advanced Research
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesLos Alamos National LaboratoryNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesUniversity of California, San DiegoNational Institute of Child Health and Human DevelopmentFlatiron HealthDivision of Chemical, Bioengineering, Environmental, and Transport SystemsSamsung Advanced Institute of TechnologySamsungNational Institutes of HealthNational Science Foundation
KeywordsSequence alignmentComputational biologySequence (biology)Protein superfamilySimilarity (geometry)Structural alignmentHomology modelingSequence homologyComputer scienceStructural similarityAlignment-free sequence analysisLoop modelingHomology (biology)Protein structureMetric (unit)Structural motifArtificial intelligenceProtein sequencingSequence motifPeptide sequenceBiologyProtein structure predictionGeneticsAmino acidGeneImage (mathematics)BiochemistryEngineering

Abstract

fetched live from OpenAlex

Exploiting sequence-structure-function relationships in biotechnology requires improved methods for aligning proteins that have low sequence similarity to previously annotated proteins. We develop two deep learning methods to address this gap, TM-Vec and DeepBLAST. TM-Vec allows searching for structure-structure similarities in large sequence databases. It is trained to accurately predict TM-scores as a metric of structural similarity directly from sequence pairs without the need for intermediate computation or solution of structures. Once structurally similar proteins have been identified, DeepBLAST can structurally align proteins using only sequence information by identifying structurally homologous regions between proteins. It outperforms traditional sequence alignment methods and performs similarly to structure-based alignment methods. We show the merits of TM-Vec and DeepBLAST on a variety of datasets, including better identification of remotely homologous proteins compared with state-of-the-art sequence alignment and structure prediction methods.

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 categoriesResearch integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.059
Threshold uncertainty score0.999

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 integrity0.0020.001
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 head0.004
GPT teacher head0.241
Teacher spread0.237 · 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