التفاصيل البيبلوغرافية
| العنوان: |
Alternative splicing events as peripheral biomarkers for motor learning deficit caused by adverse prenatal environments. |
| المؤلفون: |
Dutta, Dipankar J., Junko Sasaki, Bansal, Ankush, Keiji Sugai, Satoshi Yamashita, Guojiao Li, Lazarski, Christopher, Li Wang, Toru Sasaki, Chiho Yamashita, Carryl, Heather, Ryo Suzuki, Masato Odawara, Yuka Imamura Kawasawa, Pasko Rakic, Masaaki Torii, Kazue Hashimoto-Torii |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 12/12/2023, Vol. 120 Issue 50, p1-11, 55p |
| مصطلحات موضوعية: |
ALTERNATIVE RNA splicing, MOTOR learning, PRENATAL alcohol exposure, RNA-binding proteins, GENE expression |
| مستخلص: |
Severity of neurobehavioral deficits in children born from adverse pregnancies, such as maternal alcohol consumption and diabetes, does not always correlate with the adversity's duration and intensity. Therefore, biological signatures for accurate prediction of the severity of neurobehavioral deficits, and robust tools for reliable identification of such biomarkers, have an urgent clinical need. Here, we demonstrate that significant changes in the alternative splicing (AS) pattern of offspring lymphocyte RNA can function as accurate peripheral biomarkers for motor learning deficits in mouse models of prenatal alcohol exposure (PAE) and offspring of mother with diabetes (OMD). An aptly trained deep-learning model identified 29 AS events common to PAE and OMD as superior predictors of motor learning deficits than AS events specific to PAE or OMD. Shapley-value analysis, a game-theory algorithm, deciphered the trained deep-learning model's learnt associations between its input, AS events, and output, motor learning performance. Shapley values of the deep-learning model's input identified the relative contribution of the 29 common AS events to the motor learning deficit. Gene ontology and predictive structure-function analyses, using Alphafold2 algorithm, supported existing evidence on the critical roles of these molecules in early brain development and function. The direction of most AS events was opposite in PAE and OMD, potentially from differential expression of RNA binding proteins in PAE and OMD. Altogether, this study posits that AS of lymphocyte RNA is a rich resource, and deep-learning is an effective tool, for discovery of peripheral biomarkers of neurobehavioral deficits in children of diverse adverse pregnancies. [ABSTRACT FROM AUTHOR] |
|
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
