Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders

doi:10.1007/s12264-025-01360-0

科研成果详情

题名	Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders
作者	Yin, Huamin1,2; Wang, Zhendong3; Wang, Wenhang 2; Liu, Jiaxin 2; Xue, Yirui 4; Liu, Li 2; Shen, Jingling 2; Duan, Lian1
发表日期	2025-02-06
发表期刊	NEUROSCIENCE BULLETIN 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Neurodevelopmental disorders Fetal brain development Predicting drug candidates Pathway Entropy
其他关键词	AUTISM ; CANCER ; NEUROPATHOLOGY ; GENETICS ; TARGET
摘要	Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website (https://ndd-lab.shinyapps.io/NDDP) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
资助项目	National Natural Science Foundation of China [81701350, 31671252]; Health Technology Plan of Zhejiang Province [2023RC205]
出版者	SPRINGER
ISSN	1673-7067
EISSN	1995-8218
DOI	10.1007/s12264-025-01360-0
页数	16
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:001414793000001
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	39913063
通讯作者地址	[Duan, Lian]Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou 325000, Peoples R China. ; [Shen, Jingling]Wenzhou Univ, Inst Life Sci, Coll Life & Environm Sci, Wenzhou 325035, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/225572
专题	第一临床医学院（信息与工程学院）、附属第一医院_中心实验室附属第一医院
通讯作者	Shen, Jingling; Duan, Lian
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou 325000, Peoples R China; 2.Wenzhou Univ, Inst Life Sci, Coll Life & Environm Sci, Wenzhou 325035, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Intervent Pulmonol Zhejiang Prov, Wenzhou 325000, Peoples R China; 4.Wenzhou Med Univ, Wenzhou 325035, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
推荐引用方式 GB/T 7714	Yin, Huamin,Wang, Zhendong,Wang, Wenhang,et al. Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders[J]. NEUROSCIENCE BULLETIN,2025.
APA	Yin, Huamin., Wang, Zhendong., Wang, Wenhang., Liu, Jiaxin., Xue, Yirui., ... & Duan, Lian. (2025). Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders. NEUROSCIENCE BULLETIN.
MLA	Yin, Huamin,et al."Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders".NEUROSCIENCE BULLETIN (2025).