{"doi":"10.1016/j.celrep.2025.115402","title":"ALS molecular subtypes are a combination of cellular and pathological features learned by deep multiomics classifiers","abstract":"Amyotrophic lateral sclerosis (ALS) is a complex syndrome with multiple genetic causes and wide variation in disease presentation. Despite this heterogeneity, large-scale genomics studies revealed that ALS postmortem samples can be grouped into a small number of subtypes, defined by transcriptomic signatures of mitochondrial dysfunction and oxidative stress (ALS-Ox), microglial activation and neuroinflammation (ALS-Glia), or TDP-43 pathology and associated transposable elements (ALS-TE). In this study, we present a deep ALS neural net classifier (DANCer) for ALS molecular subtypes. Applying DANCer to an expanded cohort from the NYGC ALS Consortium highlights two subtypes that strongly correlate with disease duration: ALS-TE in cortex and ALS-Glia in spinal cord. Finally, single-nucleus transcriptomes demonstrate that ALS subtypes are recapitulated in neurons and glia, with both ALS-wide and subtype-specific alterations in all cell types. In summary, ALS molecular subtypes represent a combination of cellular and pathological features that correlate with clinical features of ALS.","journal":"Cell Reports","year":2025,"id":509759,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9297,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1365670,"name":"Regina Shaw","orcid":null,"position":1,"is_corresponding":false},{"id":1365671,"name":"Isobel Bolger","orcid":null,"position":2,"is_corresponding":false},{"id":1052008,"name":"Oliver H. Tam","orcid":"0000-0002-1023-3655","position":3,"is_corresponding":false},{"id":58926,"name":"Hemali Phatnani","orcid":"0000-0002-6571-3891","position":4,"is_corresponding":false},{"id":345342,"name":"Molly Hammell","orcid":"0000-0003-0405-8392","position":5,"is_corresponding":false},{"id":345340,"name":"Kathryn O’Neill","orcid":"0000-0002-5247-6428","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40067829","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}