همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Element-Specific Estimation of Background Mutation Rates in Whole Cancer Genomes Through Transfer Learning

نویسندگان :

ّFarideh Bahari¹ Reza Ahangari Cohan² Hesam Montazeri³

1- انستیتو پاستور ایران- 2- انستیتو پاستور ایران- 3- دانشگاه تهران

کلمات کلیدی :

background mutation rate estimation،PCAWG project،element-specific BMR modeling،transfer learning،cancer driver discovery

چکیده :

Mutational burden tests are essential for detecting signals of positive selection in cancer driver discovery by comparing observed mutation rates with background mutation rates (BMRs). However, accurate BMR estimation is challenging due to the diversity of mutational processes across genomes, complicating driver discovery efforts. Existing methods rely on various genomic regions and features for BMR estimation but lack a model that integrates both intergenic intervals and functional genomic elements on a comprehensive set of genomic features. Here, we introduce eMET (element-specific Mutation Estimator with boosted Trees), which employs 1,372 (epi)genomic features from intergenic data and fine-tunes it with element-specific data through transfer learning. Applied to PCAWG somatic mutations, eMET significantly improves BMR accuracy and has potential to enhance driver discovery. Additionally, we provide an extensive analysis of BMR estimation, examining different machine learning models, genomic interval strategies, feature categories, and dimensionality reduction techniques.

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ثمین همایش، سامانه مدیریت کنفرانس ها و جشنواره ها - نگارش 40.4.1