Periodic Reporting for period 3 - GENE-SWitCH (The regulatory GENomE of SWine and CHicken: functional annotation during development)
Periodo di rendicontazione: 2022-07-01 al 2023-12-31
To meet the demands of a growing human population, the global food system must produce healthy food using fewer natural resources while reducing environmental impact. For farm animals, the improvement of breeding strategies and management practices relies on an enhanced ability to use the genetic code (genotype) to predict the desired trait (phenotype). The main objective of GENE-SWitCH was to provide new knowledge on the functional genomes of two monogastric farm species that are major sources of meat (pigs and chickens) and to enable the immediate translation of this knowledge to the pig and poultry sectors. Three specific and interconnected objectives were pursued: (i) to improve the functional annotation of these genomes and to gain insights into the dynamics of their activity during foetal and embryonic development, (ii) to develop new knowledge and tools for precision breeding using genomic functional information, and (iii) to standardise data and processes in an open science approach (Figure), coupled with an effective programme of broad dissemination and outreach to European stakeholders. GENE-SWitCH has been part of the FAANG (Functional Annotation of Animal Genomes) initiative and a founding member of the EuroFAANG infrastructure project (https://eurofaang.eu(si apre in una nuova finestra)).
To improve the functional annotation of these genomes and to gain insights into the dynamics of their activity during foetal and embryonic development) we collected seven tissues (liver, lung, small intestine, cerebellum, skin, kidney, skeletal muscle) at three developmental stages (early organogenesis, late organogenesis, newborn) for each species. We profiled these tissues by the core molecular assays required for the functional annotation of these genomes: (i) mRNA-seq, smallRNA-seq and Iso-seq, (ii) ATAC-seq, (iii) ChIP-seq of four histone marks (H3K4me1, H3K4me3, H3K27me3, H3K27Ac), (iv) RRBS and WGBS, and (v) Promoter Capture Hi-C. We developed or adapted dedicated bioinformatic pipelines for the primary analysis of these datasets. The results allowed to enhance the functional annotation of the pig and chicken reference genome sequences, that is released via the Ensembl Genome Browser (https://www.ensembl.org/Sus_scrofa/Info/Annotation(si apre in una nuova finestra)). We undertook integrative analyses to characterize the tissue specificity and temporal dynamics of the functional elements across development (switches). We ensured data quality and accessibility in line with the FAIR (Findable, Accessible, Interoperable, Reusable) principles of open science. We developed and provided user-friendly tools for submitting, storing and visualising protocols, raw sequencing data and associated metadata, as well as results and analysis files, and developed the FAANG Ontology Improvement Service to facilitate collaborative refinement of livestock ontologies. We provided training activities like bioinformatics workshops for researchers and industry specialists to effectively exploit through Ensembl the wealth of data and tools generated by GENE-SWitCH.
To develop new knowledge and tools for precision breeding using genomic functional information, we employed two different and complementary approaches. The first was to assess the value of functional genome annotations to enhance the prediction accuracy of breeding values in commercial populations. We extended Bayesian and machine learning genomic prediction models to exploit the new genome annotation maps of pig and chicken. QTLs in chicken were fine-mapped based on a powerful advanced intercross line, and eQTL in pigs were generated and analysed from expression data in three tissues obtained from 300 pigs. Then, functional annotations and eQTLs data were used to validate the developed models. The models were finally validated in large animal commercial sets shared by the swine and poultry breeding companies collaborating in GENE-SWitCH. One major outcome was the use of FAETH (Functional And Evolutionary Trait Heritability) scores that, by leveraging several functional annotation layers, can improve predictive accuracies in pig breeding. The second approach was to identify the epigenetic effects triggered by high fibre contents in the sow diet on the pig fetus and offspring, as a basis for future nutritional studies targeting the use of lower-quality, more sustainable feed in animal breeding. Results showed that high fibre contents in sow diets determine a pervasive epigenetic alteration of the functional genome of liver and muscle in fetus and piglets; functional effects on metabolic and anti-inflammatory functions could be detected at both tissues in piglets.
We implemented an intense program of clustering activities with the other projects funded by the same H2020 call as GENE-SWitCH (BovReg, AQUA-FAANG) that resulted in useful collaborations and paved the bases to the design of the EuroFAANG infrastructure project. We carried out several activities (e.g. devise and implement the project training program, organization of workshops and webinars with industry; videos, brochures and factsheet releases) aimed to enable the use by stakeholders of the knowledge and tools produced by GENE-SWitCH for improving the effectiveness of genomic selection of the pig and poultry sectors. The final version of the project website (https://www.gene-switch.eu(si apre in una nuova finestra)) provides links to all scientific, dissemination and outreach activities of the project.
To develop new knowledge and tools for precision breeding using genomic functional information, we employed two different and complementary approaches. The first was to assess the value of functional genome annotations to enhance the prediction accuracy of breeding values in commercial populations. We extended Bayesian and machine learning genomic prediction models to exploit the new genome annotation maps of pig and chicken. QTLs in chicken were fine-mapped based on a powerful advanced intercross line, and eQTL in pigs were generated and analysed from expression data in three tissues obtained from 300 pigs. Then, functional annotations and eQTLs data were used to validate the developed models. The models were finally validated in large animal commercial sets shared by the swine and poultry breeding companies collaborating in GENE-SWitCH. One major outcome was the use of FAETH (Functional And Evolutionary Trait Heritability) scores that, by leveraging several functional annotation layers, can improve predictive accuracies in pig breeding. The second approach was to identify the epigenetic effects triggered by high fibre contents in the sow diet on the pig fetus and offspring, as a basis for future nutritional studies targeting the use of lower-quality, more sustainable feed in animal breeding. Results showed that high fibre contents in sow diets determine a pervasive epigenetic alteration of the functional genome of liver and muscle in fetus and piglets; functional effects on metabolic and anti-inflammatory functions could be detected at both tissues in piglets.
We implemented an intense program of clustering activities with the other projects funded by the same H2020 call as GENE-SWitCH (BovReg, AQUA-FAANG) that resulted in useful collaborations and paved the bases to the design of the EuroFAANG infrastructure project. We carried out several activities (e.g. devise and implement the project training program, organization of workshops and webinars with industry; videos, brochures and factsheet releases) aimed to enable the use by stakeholders of the knowledge and tools produced by GENE-SWitCH for improving the effectiveness of genomic selection of the pig and poultry sectors. The final version of the project website (https://www.gene-switch.eu(si apre in una nuova finestra)) provides links to all scientific, dissemination and outreach activities of the project.
The annotation efforts of GENE-SWitCH have greatly expanded the functional annotation of the pig and chicken genomes. Indeed, a major result of the project is the achievement of the Ensembl Regulatory Builds for pig and chicken as the first substantial public annotation of regulatory sequences in the genomes of vertebrate species other than human and mouse. An impressive amount of well-annotated and easily accessible (FAIR) genomic data is now available to researchers from different scientific fields and private companies. For example, the GENE-SWitCH datasets will be very useful for the scientific communities working on the developmental biology of these species.
GENE-SWitCH has produced important results on the value of functional genome annotations for genomic selection. The recent results on the use of FAETH scores to improve the accuracy of genomic predictions in pig breeding represent an important milestone for the further use of multiple layers of functional genome annotations to increase genomic selection accuracy. The finding that fibre-rich maternal diets have subtle but significant epigenetic effects on piglets encourages further research into sustainable fibre sources and the development of 'genome-enabled' strategies to improve the health of young farmed animals.
Overall, the project has established a strong foundation for future discoveries in farm animal genomics research and a useful reference for its use by industry. The enhancements to the FAANG data portal (Fig. 1) provide researchers with tools for querying, visualisation and customisation, facilitating deeper exploration and discovery. The ongoing EuroFAANG infrastructure project (https://eurofaang.eu(si apre in una nuova finestra)) co-founded by GENE-SWitCH, is expected to realise the full potential of genotype-to-phenotype research to improve health, welfare and other desirable traits relevant to sustainable animal production over the next decade.
GENE-SWitCH has produced important results on the value of functional genome annotations for genomic selection. The recent results on the use of FAETH scores to improve the accuracy of genomic predictions in pig breeding represent an important milestone for the further use of multiple layers of functional genome annotations to increase genomic selection accuracy. The finding that fibre-rich maternal diets have subtle but significant epigenetic effects on piglets encourages further research into sustainable fibre sources and the development of 'genome-enabled' strategies to improve the health of young farmed animals.
Overall, the project has established a strong foundation for future discoveries in farm animal genomics research and a useful reference for its use by industry. The enhancements to the FAANG data portal (Fig. 1) provide researchers with tools for querying, visualisation and customisation, facilitating deeper exploration and discovery. The ongoing EuroFAANG infrastructure project (https://eurofaang.eu(si apre in una nuova finestra)) co-founded by GENE-SWitCH, is expected to realise the full potential of genotype-to-phenotype research to improve health, welfare and other desirable traits relevant to sustainable animal production over the next decade.