Highly significant improvement of protein sequence alignments with AlphaFold2.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36130276", "kind": "science-record", "revision": 2, "content_hash": "sha256:b8dc4bfced834c8450b765a84f572916a0250aaa61d3c73359ff394f1d8c4ff6", "created_at": "2026-11-01T18:15:24Z", "updated_at": "2026-11-01T19:00:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Highly significant improvement of protein sequence alignments with AlphaFold2.", "doi": "10.1093/bioinformatics/btac625", "pmid": "36130276", "authors": ["Athanasios Baltzis", "Leila Mansouri", "Suzanne Jin", "Björn E Langer", "Ionas Erb", "Cedric Notredame"], "journal": "Bioinformatics (Oxford, England)", "year": 2022, "abstract": "MOTIVATION: Protein sequence alignments are essential to structural, evolutionary and functional analysis, but their accuracy is often limited by sequence similarity unless molecular structures are available. Protein structures predicted at experimental grade accuracy, as achieved by AlphaFold2, could therefore have a major impact on sequence analysis.\nRESULTS: Here, we find that multiple sequence alignments estimated on AlphaFold2 predictions are almost as accurate as alignments estimated on experimental structures and significantly closer to the structural reference than sequence-based alignments. We also show that AlphaFold2 structural models of relatively low quality can be used to obtain highly accurate alignments. These results suggest that, besides structure modeling, AlphaFold2 encodes higher-order dependencies that can be exploited for sequence analysis.\nAVAILABILITY AND IMPLEMENTATION: All data, analyses and results are available on Zenodo (https://doi.org/10.5281/zenodo.7031286). The code and scripts have been deposited in GitHub (https://github.com/cbcrg/msa-af2-nf) and the various containers in (https://cloud.sylabs.io/library/athbaltzis/af2/alphafold, https://hub.docker.com/r/athbaltzis/pred).\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "claims": [{"id": "claim-data-access", "statement": "All data, analyses and results are available on Zenodo (https://doi.org/10.5281/zenodo.7031286).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36130276", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "All data, analyses and results are available on Zenodo (https://doi.org/10.5281/zenodo.7031286)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Alignments computed from AlphaFold2 predictions achieved an average SoP accuracy of 93.95%, compared with 70.33% for sequence-based alignments, an improvement of 23.62 percentage points.", "kind": "quantitative", "target": {"value": 0.0002, "unit": "p-value", "tolerance": null, "source": "Across all MSAs, the difference is highly significant, with an average improvement by 23.62 percent points of MSA-AF2 over MSA-Seq (93.95% versus 70.33% and Wilcoxon test p-value = 0.0002, Table 1, Supplementary Table S1a)."}, "evidence": [{"asset": "source:pmid:36130276", "locator": "sections[11] \"3.1 Alignments computation and comparisons\" paragraph 2", "quote": "Across all MSAs, the difference is highly significant, with an average improvement by 23.62 percent points of MSA-AF2 over MSA-Seq (93.95% versus 70.33% and Wilcoxon test p-value = 0.0002, Table 1, Supplementary Table S1a)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Alignments computed from AlphaFold2 predictions achieved an average SoP accuracy of 93.95%, compared with 70.33% for sequence-based alignments, an improvement of 23.62 percentage points.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36130276"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36130276", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioinformatics/btac625", "sha256": "sha256:0786c8b87fc7075214118cd3cfd0c6a09230a4ed2d2c97eb6896be0f63c98c8c", "bytes": 29186, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioinformatics/btac625", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9665868", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "absent", "methods": [], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": null, "expected_value": 0.0002, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method", "operations"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All data, analyses and results are available on Zenodo (https://doi.org/10.5281/zenodo.7031286)."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:36130276"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:06:32Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8772, "completion_tokens": 1826, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36130276", "type": "paper", "label": "pmid:36130276"}, {"id": "source:pmid:36130276", "type": "manuscript", "label": "PMID 36130276 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36130276", "type": "paper", "label": "pmid:36130276"}, {"id": "source:pmid:36130276", "type": "manuscript", "label": "PMID 36130276 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36130276", "type": "extraction", "used": ["source:pmid:36130276"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36130276", "parent_hash": "sha256:95db9486b036edf6632d3f6113594d6dcc83ddb82133dcf66ae213d523202edc", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"]}