{"id":477,"title":"A compact motif vocabulary is differentially interpreted across human cell types","title_zh":"紧凑的基序词汇在人类不同细胞类型中被差异解读","url":"https://biorxiv.org/content/10.64898/2026.11.01.763377v1","doi":"10.64898/2026.11.01.763377","pmid":null,"journal":"biorxiv","kind":"preprint","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:19+00:00","authors":["Shen, S.","Wang, W."],"primary_topic":"ai-compute","topics":[{"slug":"ethics-policy","score":2.0,"hits":["regulation","regulatory"]},{"slug":"ai-compute","score":1.0,"hits":["neural network"]},{"slug":"omics-methods","score":1.0,"hits":["chip-seq"]}],"topic_score":2.0,"preference_score":0.0,"preference_labels":[],"llm_score":68.0,"final_score":68.0,"score_dims":{"novelty":85,"rigor":75,"impact":60,"relevance":30,"translation":35},"recommend_reason":"方法学和调控基因组学概念上有新意，对理解顺式调控语法与AI模型可解释性有价值；但与生殖医学、胚胎和ART核心问题距离较远，适合关注计算调控组学的读者浏览。","keywords":["CNN-CR","顺式调控基序","基因表达预测","染色质状态","调控变异"],"selected":1,"story_id":118,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"biorxiv-devbio","source_name":"bioRxiv · 发育/细胞/基因组学（领域过滤）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"biorxiv","journal_tier":"standard","journal_if":null,"is_mock":false,"summary_zh":"该预印本研究开发可解释神经网络CNN-CR，在116个人类生物样本中预测基因表达并学习调控基序。结果显示启动子调控高度可压缩：数十个重复基序家族即可保留大型细胞类型特异性词汇的大部分预测信息，并能泛化到发现集之外的细胞背景；这些基序结合位点保守，且富集于精细定位的调控变异。细胞背景通过两层机制起作用：染色质状态决定哪些基序实例可用，reader身份决定可及基序如何被解读；ChIP-seq显示reader占据跨细胞类型频繁变化，基因组尺度扰动支持相应的背景依赖功能。结论是调控多样性可源于对紧凑共享DNA词汇的差异可及与解读。","summary":"How a common genome generates diverse human cell types may depend less on distinct cis-regulatory vocabularies than on context-dependent use of a shared one. We have developed CNN-CR, an interpretable neural network that learns regulatory motifs while predicting gene expression across 116 human biosamples. Promoter regulation proves highly compressible: dozens of recurrent motif families retain most of the predictive information of much larger cell-type-specific vocabularies and generalize to cellular contexts excluded from their discovery. These motifs are conserved at their binding sites and enriched at fine-mapped regulatory variants. Cellular context acts at two levels: chromatin state gates which motif instances are available for regulatory use, whereas reader identity determines how accessible motifs are interpreted. ChIP-seq data reveal frequent shifts in reader occupancy across cell types, and genome-scale perturbations support corresponding context-dependent reader functions. Thus, regulatory diversity can emerge through differential access to and interpretation of a compact shared DNA vocabulary.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}