Characterizing Multimodal Mutational Processes in Cancer Using MOTET

MOTET jointly infers multimodal mutational processes in 2,583 PCAWG whole genomes, recovering known MPs more accurately than standard post hoc correlation methods.

• Why it matters: Mutational signatures across SBSs, DBSs, and small IDs are often inferred separately and then linked afterward, masking shared mechanisms that coordinate patterns across modalities.
• What they did: MOTET is a Bayesian framework that defines a Mutational Process as a unified latent activity and jointly infers coupled signatures across mutation modalities in PCAWG whole genomes.
• The result: MOTET links an SBS37-related signature with a TG>CA-dominated DBS component and splits canonical SBS12-like activity into two MPs with distinct tissue distributions, enabling more integrated discovery.

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