Sharma Omveer, Nayak Ritu, Mizrahi Liron, Rike Wote Amelo, Choudhary Ashwani, Sadis Hagit, Hussein Yara, Rosh Idan, Tripathi Utkarsh, Shemen Aviram, Stern Yam, Squassina Alessio, Alda Martin, Stern Shani
Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Transl Psychiatry. 2025 Sep 3;15(1):339. doi: 10.1038/s41398-025-03573-3.
This research aimed to develop a machine learning algorithm to predict suicide risk in bipolar disorder (BD) patients using RNA sequencing analysis of lymphoblastoid cell lines (LCLs). By identifying differentially expressed genes (DEGs) between high and low risk patients and their enrichment in relevant pathways, we gained insights into the molecular mechanisms underlying suicide risk. LCL gene expression analysis revealed pathway enrichment related to primary immunodeficiency, ion channels, and cardiovascular defects. Notably, genes such as LCK, KCNN2, and GRIA1 emerged as pivotal, suggesting their potential roles as biomarkers. Machine learning algorithms trained on a subset of the patients and tested on others demonstrated high accuracy in distinguishing low and high risk of suicide in BD patients. Additionally, the study explored the genetic overlap between suicide-related genes and several psychiatric disorders. Our study enhances the understanding of the complex interplay between genetics and suicidal behaviour, providing a foundation for prevention strategies.
本研究旨在开发一种机器学习算法,通过对淋巴母细胞系(LCLs)进行RNA测序分析来预测双相情感障碍(BD)患者的自杀风险。通过识别高风险和低风险患者之间的差异表达基因(DEGs)及其在相关途径中的富集情况,我们深入了解了自杀风险背后的分子机制。LCL基因表达分析揭示了与原发性免疫缺陷、离子通道和心血管缺陷相关的途径富集。值得注意的是,诸如LCK、KCNN2和GRIA1等基因成为关键基因,表明它们作为生物标志物的潜在作用。在一部分患者上训练并在其他患者上测试的机器学习算法在区分BD患者的低自杀风险和高自杀风险方面表现出高精度。此外,该研究还探索了自杀相关基因与几种精神疾病之间的遗传重叠。我们的研究增进了对遗传学与自杀行为之间复杂相互作用的理解,为预防策略奠定了基础。