Over the course of the project, we:
• Generated the first comprehensive genome-wide catalog of cardiac micropeptides in humans and rats.
• Identified 339 micropeptides encoded by lncRNAs in human hearts and over 1,000 micropeptides from 5’UTRs of canonical mRNAs.
• Published our human dataset in Cell (2019), rat dataset in Genome Biology (2021), and co-led the inclusion of micropeptide annotations into GENCODE, published in Nature Biotechnology (2022).
• Performed high-resolution single-nucleus and single-cell RNA sequencing of 14 human hearts (Nature, 2020), revealing cell-type-specific expression patterns.
• Identified micropeptides with mitochondrial localization, potential secretory roles, and others with transmembrane domains, suggesting diverse functionality.
• Found over 500 primate-specific micropeptides using an innovative evolutionary pipeline and comparative translatome analysis (Nature Cardiovascular Research, 2024).
• Validated micropeptide-protein interactions via high-throughput PRISMA screens (Molecular Cell, 2023), showing relevance in translation, endocytosis, and splicing.
• Conducted a pooled CRISPR screen across 169 translated lncRNAs, with downstream phenotyping in iPSC-derived cardiomyocytes, uncovering regulatory lncRNAs like LINC01405.
Exploitation of Results
• Our micropeptide catalogs and methodologies have been made openly available, serving as a valuable resource for basic researchers, bioinformaticians, and clinicians working in cardiac and translational genomics.
• The standardized annotations in GENCODE-Ensembl and UniProt provide the foundation for clinical genome interpretation, especially in the context of rare genetic diseases and cardiomyopathies.
• Micropeptides identified with functional effects on mitochondrial activity and protein synthesis are now being considered as pre-clinical targets for therapeutic development.
• Our computational pipeline for evolutionary annotation has been integrated into collaborative platforms and can now be used by other labs for species-specific gene discovery.
• Intellectual property generated (e.g. around candidate therapeutic micropeptides) is currently under review for patent protection and potential industry partnerships.
Dissemination of Results
• We published peer-reviewed articles in high-impact journals (Cell, Nature, Nature Biotechnology, Molecular Cell, etc.).
• Our team presented results at major conferences in cardiology, functional genomics, and translational biology.
• All major datasets and tools were deposited in open-access repositories (e.g. GEO, ProteomeXchange, ENA) and linked to web-based tools enabling community use.
• Through our international consortium efforts, we engaged over 65 collaborators worldwide, laying the groundwork for sustained dissemination and future funding proposals.
• Workshops and training sessions were held to support early-career scientists and data users in using ribosome profiling and our evolutionary tools.
