Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson^® to sieve through all RBPs in the genome and identify new RBPs linked to ALS (ALS-RBPs). IBM Watson extracted features from published literature to create semantic similarities and identify new connections between entities of interest. IBM Watson analyzed all published abstracts of previously known ALS-RBPs, and applied that text-based knowledge to all RBPs in the genome, ranking them by semantic similarity to the known set. We then validated the Watson top-ten-ranked RBPs at the protein and RNA levels in tissues from ALS and non-neurological disease controls, as well as in patient-derived induced pluripotent stem cells. 5 RBPs previously unlinked to ALS, hnRNPU, Syncrip, RBMS3, Caprin-1 and NUPL2, showed significant alterations in ALS compared to controls. Overall, we successfully used IBM Watson to help identify additional RBPs altered in ALS, highlighting the use of artificial intelligence tools to accelerate scientific discovery in ALS and possibly other complex neurological disorders.

肌萎缩性侧索硬化症（ALS）是一种破坏性神经退行性疾病，没有有效的治疗方法。已经显示出许多RNA结合蛋白（RBPs）在ALS中发生了改变，其中11个RBPs发生了突变，导致该家族性疾病，还有6个RBPs在ALS中表现出异常的表达/分布，尽管没有任何已知的突变。RBP失调被广泛认为是ALS病理生物学的一个促成因素。人类基因组中至少有1542个RBP。因此，其他未知的RBP也可能与ALS的发病机制有关。我们使用IBM沃森^®筛选出基因组中的所有RBP，并鉴定与ALS（ALS-RBP）相关的新RBP。IBM Watson从已发表的文献中提取了特征，以创建语义相似性并确定感兴趣的实体之间的新连接。IBM Watson分析了先前已知的ALS-RBP的所有已发布摘要，并将基于文本的知识应用于基因组中的所有RBP，并根据与已知集合的语义相似性对其进行了排名。然后，我们在ALS和非神经疾病对照组织以及患者衍生的多能干细胞的组织中，在蛋白质和RNA水平上验证了Watson排名前十的RBP。与对照相比，先前未与ALS，hnRNPU，Syncrip，RBMS3，Caprin-1和NUPL2关联的5个RBP显示了ALS的显着改变。总体而言，我们成功地使用了IBM Watson来帮助确定ALS中已更改的其他RBP，