{"id":"https://openalex.org/W7225630455","doi":"https://doi.org/10.64898/2026.10.29.762727","title":"MELD: Mutation Effect Learning through Differential embeddings","display_name":"MELD: Mutation Effect Learning through Differential embeddings","publication_year":2026,"publication_date":"2026-11-09","ids":{"openalex":"https://openalex.org/W7225630455","doi":"https://doi.org/10.64898/2026.10.29.762727"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.29.762727","doi":"https://doi.org/10.64898/2026.10.29.762727","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.762727","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/09/2026.10.29.762727.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/09/2026.10.29.762727.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5161330128","display_name":"Aliaa Alajji","orcid":"https://orcid.org/0009-0003-2249-702X","observed_orcids":["https://orcid.org/0009-0003-2249-702X"]},"institutions":[{"id":"https://openalex.org/I60342839","display_name":"Qatar University","ror":"https://ror.org/00yhnba62","country_code":"QA","type":"education","lineage":["https://openalex.org/I60342839"]}],"countries":["QA"],"is_corresponding":false,"raw_author_name":"Aliaa Alajji","raw_affiliation_strings":["Qatar University;"],"raw_orcid":"https://orcid.org/0009-0003-2249-702X","affiliations":[{"raw_affiliation_string":"Qatar University;","institution_ids":["https://openalex.org/I60342839"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161331137","display_name":"Raihan Jashil","orcid":"https://orcid.org/0009-0004-5811-5545","observed_orcids":["https://orcid.org/0009-0004-5811-5545"]},"institutions":[{"id":"https://openalex.org/I4210136017","display_name":"University of Doha for Science and Technology","ror":"https://ror.org/041ddxq18","country_code":"QA","type":"education","lineage":["https://openalex.org/I4210136017"]}],"countries":["QA"],"is_corresponding":false,"raw_author_name":"Raihan Jashil","raw_affiliation_strings":["University of Doha for Science and Technology;"],"raw_orcid":"https://orcid.org/0009-0004-5811-5545","affiliations":[{"raw_affiliation_string":"University of Doha for Science and Technology;","institution_ids":["https://openalex.org/I4210136017"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055826525","display_name":"Raghvendra Mall","orcid":"https://orcid.org/0000-0003-1779-3150","observed_orcids":["https://orcid.org/0000-0003-1779-3150"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Raghvendra Mall","raw_affiliation_strings":["Qatar Computing Research Institute"],"raw_orcid":"https://orcid.org/0000-0003-1779-3150","affiliations":[{"raw_affiliation_string":"Qatar Computing Research Institute","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5058586894","display_name":"Mohamed Mokhtar Elshrif","orcid":"https://orcid.org/0000-0003-0092-8258","observed_orcids":["https://orcid.org/0000-0003-0092-8258"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Mohamed Elshrif","raw_affiliation_strings":["Qatar Computing Research Institute"],"raw_orcid":"https://orcid.org/0000-0003-0092-8258","affiliations":[{"raw_affiliation_string":"Qatar Computing Research Institute","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5058586894"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.9818999767303467,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.9818999767303467,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12254","display_name":"Machine Learning in Bioinformatics","score":0.00430000014603138,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.00430000014603138,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/single-nucleotide-variants","display_name":"single nucleotide variants","score":0.8820000290870667},{"id":"https://openalex.org/keywords/in-silico-mutagenesis","display_name":"in silico mutagenesis","score":0.8560000061988831},{"id":"https://openalex.org/keywords/clinvar","display_name":"ClinVar","score":0.6000000238418579},{"id":"https://openalex.org/keywords/brca1","display_name":"BRCA1","score":0.6119999885559082},{"id":"https://openalex.org/keywords/genome-editing","display_name":"genome editing","score":0.48500001430511475}],"concepts":[{"id":"https://openalex.org/C93226319","wikidata":"https://www.wikidata.org/wiki/Q193137","display_name":"Differential (mechanical device)","level":2,"score":0.49219998717308044},{"id":"https://openalex.org/C3019921246","wikidata":"https://www.wikidata.org/wiki/Q104853310","display_name":"Differential effects","level":2,"score":0.4880000054836273},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.46619999408721924},{"id":"https://openalex.org/C16318435","wikidata":"https://www.wikidata.org/wiki/Q149299","display_name":"Mutagenesis","level":4,"score":0.4571000039577484},{"id":"https://openalex.org/C151956035","wikidata":"https://www.wikidata.org/wiki/Q1132755","display_name":"Logistic regression","level":2,"score":0.4569999873638153},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.4510999917984009},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4259999990463257},{"id":"https://openalex.org/C153209595","wikidata":"https://www.wikidata.org/wiki/Q501128","display_name":"Single-nucleotide polymorphism","level":4,"score":0.4237000048160553},{"id":"https://openalex.org/C177148314","wikidata":"https://www.wikidata.org/wiki/Q170084","display_name":"Generalization","level":2,"score":0.4212999939918518},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4034999907016754},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.38100001215934753},{"id":"https://openalex.org/C12725497","wikidata":"https://www.wikidata.org/wiki/Q810247","display_name":"Baseline (sea)","level":2,"score":0.35600000619888306},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3492000102996826},{"id":"https://openalex.org/C140331021","wikidata":"https://www.wikidata.org/wiki/Q1868104","display_name":"Logit","level":2,"score":0.3481999933719635},{"id":"https://openalex.org/C3018023364","wikidata":"https://www.wikidata.org/wiki/Q425265","display_name":"Significant difference","level":2,"score":0.3458000123500824},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.33250001072883606},{"id":"https://openalex.org/C51632099","wikidata":"https://www.wikidata.org/wiki/Q3985153","display_name":"Training set","level":2,"score":0.33230000734329224},{"id":"https://openalex.org/C150899416","wikidata":"https://www.wikidata.org/wiki/Q1820378","display_name":"Transfer of learning","level":2,"score":0.3264999985694885},{"id":"https://openalex.org/C164226766","wikidata":"https://www.wikidata.org/wiki/Q7293202","display_name":"Rank (graph theory)","level":2,"score":0.3149000108242035},{"id":"https://openalex.org/C512185932","wikidata":"https://www.wikidata.org/wiki/Q28745","display_name":"Nucleotide","level":3,"score":0.3037000000476837},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.3018999993801117},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.2930000126361847},{"id":"https://openalex.org/C153180895","wikidata":"https://www.wikidata.org/wiki/Q7148389","display_name":"Pattern recognition (psychology)","level":2,"score":0.27469998598098755},{"id":"https://openalex.org/C109129352","wikidata":"https://www.wikidata.org/wiki/Q7426583","display_name":"Saturated mutagenesis","level":4,"score":0.27410000562667847},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.27309998869895935},{"id":"https://openalex.org/C189430467","wikidata":"https://www.wikidata.org/wiki/Q7293293","display_name":"Ranking (information retrieval)","level":2,"score":0.2676999866962433},{"id":"https://openalex.org/C2778755073","wikidata":"https://www.wikidata.org/wiki/Q10858537","display_name":"Scale (ratio)","level":2,"score":0.2628999948501587},{"id":"https://openalex.org/C98045186","wikidata":"https://www.wikidata.org/wiki/Q205663","display_name":"Process (computing)","level":2,"score":0.2615000009536743},{"id":"https://openalex.org/C105054674","wikidata":"https://www.wikidata.org/wiki/Q3707381","display_name":"Mean difference","level":3,"score":0.2524999976158142}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.29.762727","doi":"https://doi.org/10.64898/2026.10.29.762727","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.762727","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/09/2026.10.29.762727.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.29.762727","doi":"https://doi.org/10.64898/2026.10.29.762727","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.762727","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/09/2026.10.29.762727.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.5683000087738037,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225630455.pdf","grobid_xml":"https://content.openalex.org/works/W7225630455.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7207753196","https://openalex.org/W4410798438","https://openalex.org/W7215037267","https://openalex.org/W3177252166","https://openalex.org/W7223651511","https://openalex.org/W4303671988","https://openalex.org/W7203578191","https://openalex.org/W7160861131","https://openalex.org/W7203650487","https://openalex.org/W7215107995"],"abstract_inverted_index":{"We":[0],"introduce":[1],"MELD":[2,79,120,194],"(Mutation":[3],"Effect":[4],"Learning":[5],"through":[6,66],"Differential":[7],"Embeddings),":[8],"a":[9,98,102,110,131,145,196,219],"compact":[10],"model":[11],"for":[12,130,161,165],"predicting":[13],"the":[14,26,71,76,82,93,139,176],"functional":[15],"consequences":[16],"of":[17,46,126,141,199],"single":[18],"nucleotide":[19],"variants":[20,63],"(SNVs)":[21],"by":[22],"training":[23,77,172],"directly":[24],"on":[25,57,180],"wild-type":[27],"(WT)":[28],"versus":[29,128],"mutant":[30],"differential.":[31],"Interpreting":[32],"SNVs":[33],"is":[34,218],"central":[35],"to":[36,44,209,223],"clinical":[37],"genomics,":[38],"yet":[39],"experimental":[40],"characterization":[41],"cannot":[42],"scale":[43],"millions":[45],"observed":[47],"variants.":[48,187],"Leading":[49],"sequence-to-function":[50],"models":[51,152],"(Enformer,":[52],"Borzoi,":[53],"AlphaGenome)":[54],"are":[55],"trained":[56,179],"absolute":[58],"genomic":[59],"tracks":[60],"and":[61,109,163,204],"score":[62],"post":[64],"hoc":[65],"in-silico":[67],"mutagenesis":[68],"(ISM),":[69],"so":[70],"WT-mutant":[72],"difference":[73,84],"never":[74],"enters":[75],"loss.":[78],"instead":[80],"places":[81],"logit":[83],"\u0394z":[85],"=":[86],"z":[87,90],"mut":[88],"\u2212":[89],"wt":[91],"inside":[92],"supervised":[94],"objective.":[95],"It":[96],"combines":[97],"shared":[99,146],"CNN-Transformer":[100],"encoder,":[101],"mutant-specific":[103],"mutation-mask":[104],"boost,":[105],"multiscale":[106],"mutation-centered":[107],"pooling,":[108],"learned":[111],"adaptive":[112],"amplification":[113],"factor":[114],"\u03b1.":[115],"On":[116,144,188],"ClinVar":[117,205],"(1.57M":[118],"variants),":[119],"(1.9M":[121],"parameters)":[122],"reached":[123],"an":[124],"AUROC":[125],"0.986":[127],"0.800":[129],"same-data,":[132],"same-backbone":[133],"ISM":[134,177,225],"baseline,":[135],"with":[136,153,227],"ablations":[137],"confirming":[138],"contribution":[140],"each":[142],"component.":[143],"benchmark,":[147],"it":[148,174,208],"outperformed":[149],"frozen":[150,193],"foundation":[151],"3-1,300x":[154],"more":[155],"parameters":[156],"(AUROC":[157,183],"0.967":[158],"vs.":[159,185],"0.924":[160],"AlphaGenome":[162],"0.936":[164],"Nucleotide":[166],"Transformer).":[167],"With":[168],"only":[169],"50,":[170],"000":[171],"variants,":[173],"exceeded":[175],"baseline":[178],"all":[181],"1.48M":[182],"0.903":[184],"0.796)":[186],"BRCA1":[189],"saturation":[190],"genome":[191],"editing,":[192],"achieved":[195],"Spearman":[197],"\u03c1":[198],"0.42,":[200],"above":[201],"Borzoi":[202],"(0.40),":[203],"transfer":[206],"raised":[207],"0.45.":[210],"These":[211],"results":[212],"demonstrate":[213],"that":[214],"direct":[215],"differential":[216],"supervision":[217],"compact,":[220],"data-efficient":[221],"alternative":[222],"post-hoc":[224],"scoring":[226],"substantially":[228],"larger":[229],"pretrained":[230],"models.":[231]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}