Objectives

The overall BovReg objective is to generate and validate functional genome data and standardized analysis technologies based on all FAANG core assays, providing a catalogue of functionally active genomic features relevant to phenotypic diversity and plasticity in cattle.

BovReg will focus on three key phenotypic traits: biological efficiency (nutrient conversion, greenhouse gas emission), disease susceptibility (mastitis) and robustness (fertility) in dairy and beef cattle.

Specific objectives are:

• Establish laboratory and bioinformatics tools for functional annotation of the bovine genome and in other species or for further applications (vaccine development, cell-based bioreactors)

a) Establish six cell lines relevant for BovReg key traits, improve workflows for ChIP-seq, and validate the novel experimental laboratory tools as essential resources for benchmarking and validation of (future) research on functionally active genomic regions in livestock before and after project end.

b) Develop standardised, validated procedures (raw data quality control and processing, data retrieval from databases, data analysis algorithms) integrating existing bioinformatics tools and experimental data into genomic functional annotation pipelines to allow interoperability across datasets and consortia. The procedures will comply with FAANG and ELIXIR requirements.

c) Develop an annotation framework allowing the full interoperability of data and pipelines. These pipelines will be standardized to deploy across all possible computational platforms. The combined interoperability and normalization will ensure that data annotation can be reproduced, compared and added to incrementally. The design of very robust procedures relying on public resources will ensure the long-term sustainability of this bioinformatics infrastructure, well beyond the timeframe of the project.

• Annotate functionally active genomic regions in the bovine genome based on a comprehensive catalogue of 24 tissues that are highly relevant for the BovReg target traits, five ontogenetic stages, both gender and six new cell lines from dairy and beef breeds.
• Map functional parameters (ranging from transcriptome to intermediate phenome to phenotype) to newly annotated genomic features

a) Identify and functionally validate candidate regulatory variants that modulate the BovReg key complex phenotypic traits and molecular phenotypes (gene expression, metabolomic profiles).

b) Annotate epigenomic signatures associated with climate change and metabolic stress while considering inter- and trans-generational paternal transmission.

c) Conduct comparative genomic analysis across species to reveal sites evolving in a non-neutral way (positive selection for recent adaptation, purifying selection for key functional features).

• Develop prototype models for integrating biological knowledge on regulatory variation in the bovine genome (biology-driven genomic prediction (bd-GP) tools) into genomic selection schemes for local and global beef and dairy cattle breeds.
• Provide targeted training, dissemination and communication activities (three training courses, three session workshops associated with scientific conferences, three stakeholder workshops) in the use of the new resources and knowledge, made widely available through open access, applying FAIR principles to ensure reproducibility and ensure long-term data storage.
• Develop a Democs card game to engage with lay publics and stakeholders on issues related to livestock breeding and genomics, and establish an ethical framework for scientific and corporate cultures to ensure that the science developed is responsive to these processes.