Source: AGRICULTURAL RESEARCH SERVICE submitted to NRP
RUMINANT T2T WORKSHOP 2023
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1029749
Grant No.
2023-67015-39000
Cumulative Award Amt.
$45,300.00
Proposal No.
2022-10599
Multistate No.
(N/A)
Project Start Date
Jan 15, 2023
Project End Date
Jan 14, 2025
Grant Year
2023
Program Code
[A1201]- Animal Health and Production and Animal Products: Animal Breeding, Genetics, and Genomics
Recipient Organization
AGRICULTURAL RESEARCH SERVICE
(N/A)
BROOKINGS,SD 57006
Performing Department
(N/A)
Non Technical Summary
The first genome assembly for a mammalian genome was described in the year 2000 upon release of the human genome draft. This draft was far from complete, and in the ensuing 20 years incremental improvements have been made to the public assembly. In spring 2022, a group of researchers reported the first truly complete, "telomere to telomere" (T2T) assembly that featured an unbroken sequence with no gaps or uncertain sequences. Associated analyses revealed the scope of information that had been previously missed using less complete versions of the human genome, including addition of thousands of previously undescribed genes. Subsequent unpublished reports have demonstrated the value of comparative analysis between closely related species. The ruminant group of organisms, that includes cattle, sheep, and goat as well as a variety of deer and antelope species, is of interest for agricultural as well as evolutionary reasons. We believe that comparisons between complete genomes of ruminant species will inform our understanding of their evolution, shed light on genomic consequences of domestication, and enhance understanding of functional roles of all of the DNA in the genome. The workshop is intended to provide a platform for the human T2T research community to transfer knowledge and expertise in a focused forum beyond that possible in less focused scientific conferences.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3043399108010%
3043499108010%
3043699108010%
3043820108010%
3043999108060%
Goals / Objectives
Genome assemblies have increased in both quality and contiguity over the past 20 years, but the ultimate goal of a complete, gapless assembly including all euchromatin and heterochromatin for every chromosome of a mammalian species has been elusive. Technological advances in DNA sequencing and assembly algorithms have finally produced a complete "telomere to telomere" (T2T) genome assembly for humans from a special diploid human cell line in which both copies of each chromosome are identical. A series of papers in March 2022 presented the technology for completion of the genome and detailed analyses that the complete assembly made possible. The ad hoc group of researchers that achieved this milestone blazed a trail of technical and analytical advancements which can now be applied to other species. A recent human T2T conference (August 2022) celebrated the accomplishment and presented newer data extending the technology to true diploid samples and detailing the knowledge gained by comparing T2T assemblies of primate species. The purpose of the present proposal is to support a workshop for researchers interested in ruminant species for agriculture, conservation, and evolution, to learn from the human T2T effort. The proposed, highly focused workshop will bring together these researchers along with some of the pioneers from the human effort to enable transferal of the knowledge and skills while the enthusiasm from the human project remains high. The goals of the workshop are to launch a "Ruminant T2T" project, establishbest practices for creating complete genome assemblies, conceiveanalysis goals, determine sample types/characteristicsand data generation required to support each proposed analysis, and form teams to prosecute the analyses,
Project Methods
The workshop will be held February 23 & 24, 2023 at the USDA Meat and Animal Research Center (USMARC) in Clay Center, Nebraska, and we anticipate approximately 40-50 total attendees. The location selection is based on the historical role of USMARC in livestock genome assembly, the fact that the institution has generated the recommended data for species of agricultural importance (cattle, sheep, goat, and pig), and the fact the concept was developed by Dr. Smith who is based at that location. In our view, detaching the workshop from any coincident conferences will enhance the interactions and informal nature of the discussions to produce more active outcomes. Furthermore, holding this conference at USMARC will reduce the venue and technology associated expenses. Finally, the venue will provide the opportunity for others to meet and interact with agricultural animal scientists and see the research station and available technologies.2. Overview of Conference TopicsSpecific topics to be addressed at the workshop include:a. Latest advancements in technology and procedures and their impact on T2T assemblyb. Best practices for implementation of Verkko or alternative assemblers specific for T2T of mammalian, diploid species.c. Most efficient means to move from contigs to finished genomes, i.e. "untangling" graphs and assigning rDNA arrays and HOR appropriately.d. Making use of DNA base modification data generated by sequencinge. Impactful orthogonal assays (e.g. 3D chromatin modeling; chromatin states; transcript abundances)f. Most fruitful avenues of T2T assembly analysis and comparisons between speciesg. Discussions of sample procurement/availability for non-livestock ruminant species, including prioritization based on impact and practicability.h. Development of working groups to address each species, conduct orthogonal data production, perform analyses.

Progress 01/15/24 to 01/14/25

Outputs
Target Audience:The target audience was scientists, postdoctoral associates, and doctoral students interested in joing the Ruminant T2T Consoritum and using comparative genomics to evaluate the impact of genetic variation in livestock genomes on production traits. The workshop assembled a focused group of 44 in-person attendees and 61 simultaneous zoom participants, including representatives of 38 unique institutions from 19 countries. The target audience has since expanded to include 176 project participants, among >1000 scientists that attended subsequent presentations at two Plant and Animal Genome conferences and the Advances in Genome Biology and Technology -- Agriculture conference. In addition, a "white paper" announcing the project was published in the prominent journalNature Genetics. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The workshop included more than a dozen students/postdoctoral trainees in person and an unknown number online. Sincethe workshop, a number (more than 20, not sure of exact count) of students and early career researchers have entered thecollaboration and begun to learn the processes of genome assembly and analysis under expert guidance of establishedresearchers from the human genome community. The Project Director also arranged for training sessions both in-person (at the Advances and Genome Biology and Technology -- Agriculture Conference in March 2024) and online (via zoom in August 2024) to instruct students and interested faculty in the process of creating final T2T assemblies. How have the results been disseminated to communities of interest?A white paper has been published in the journalNature Genetics?and featured on the cover of the August 2024 edition it was published in. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The workshop was held as planned and featured thirteen plenary speakers, a networking dinner, and breakout groups forcollaboration planning. There were 44 in-person attendees and maximum 61 simultaneous zoom participants. The totalattendance included representatives of 38 unique institutions from 19 countries. A plan to encourage collaboration versuscompetition in the field was developed and the attendees charged with helping spread the word. A "white paper" was published in the prestigious journalNature Geneticsin August 2024 and featured on the cover of the issue in which it was published with the caption "on the road to ruminant T2T genomics". A consortium including 176 participants from around the globe has now generated complete genomes for giraffe (submitted to GenBank) and bighorn sheep (GenBank accession GCF_042477335.2), with 23 other species having genomes with data collected and assembly/curation in progress.

Publications

  • Type: Peer Reviewed Journal Articles Status: Published Year Published: 2024 Citation: Nature Genetics 56:1566-1573. August 2024


Progress 01/15/23 to 01/14/25

Outputs
Target Audience:The target audience was scientists, postdoctoral associates, and doctoral students interested in joing the Ruminant T2T Consoritum and using comparative genomics to evaluate the impact of genetic variation in livestock genomes on production traits. The workshop assembled a focused group of 44 in-person attendees and 61 simultaneous zoom participants, including representatives of 38 unique institutions from 19 countries. The target audience has since expanded to include 176 project participants, among >1000 scientists that attended subsequent presentations at two Plant and Animal Genome conferences and the Advances in Genome Biology and Technology -- Agriculture conference. In addition, a "white paper" announcing the project was published in the prominent journal Nature Genetics. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The workshop included more than a dozen students/postdoctoral trainees in person and an unknown number online. Since the workshop, a number (more than 20, not sure of exact count) of students and early career researchers have entered the collaboration and begun to learn the processes of genome assembly and analysis under expert guidance of established researchers from the human genome community. The Project Director also arranged for training sessions both in-person (at the Advances and Genome Biology and Technology -- Agriculture Conference in March 2024) and online (via zoom in August 2024) to instruct students and interested faculty in the process of creating final T2T assemblies. How have the results been disseminated to communities of interest?A white paper has been published in the journal Nature Genetics ?and featured on the cover of the August 2024 edition it was published in. What do you plan to do during the next reporting period to accomplish the goals?{Nothing to report}

Impacts
What was accomplished under these goals? The workshop was held as planned and featured thirteen plenary speakers, a networking dinner, and breakout groups for collaboration planning. There were 44 in-person attendees and maximum 61 simultaneous zoom participants. The total attendance included representatives of 38 unique institutions from 19 countries. A plan to encourage collaboration versus competition in the field was developed and the attendees charged with helping spread the word. A "white paper" was published in the prestigious journal Nature Genetics in August 2024 and featured on the cover of the issue in which it was published with the caption "on the road to ruminant T2T genomics". A consortium including 176 participants from around the globe has now generated complete genomes for giraffe (submitted to GenBank) and bighorn sheep (GenBank accession GCF_042477335.2), with 23 other species having genomes with data collected and assembly/curation in progress.

Publications

  • Type: Peer Reviewed Journal Articles Status: Published Year Published: 2024 Citation: Nature Genetics 56:1566-1573. August 2024


Progress 01/15/23 to 01/14/24

Outputs
Target Audience:Researchers using genomics to improve livestock, or to study chromosomal and organismal evolution. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The workshop included more than a dozen students/postdoctoral trainees in person and an unknown number online. Since the workshop, a number (more than 10, not sure of exact count) of students and early career researchers have entered the collaboration and begun to learn the processes of genome assembly and analysis under expert guidance of established researchers from the human genome community. How have the results been disseminated to communities of interest?The white paper has been submitted for publication in a journal with open access option. What do you plan to do during the next reporting period to accomplish the goals?Report on the workshop and ongoing activities at three major conferences focused on genome research, as well as the white paper publication. Release the initial "complete" genomes to the public first through GenomeArk to support community quality assessment and collaborative annotation and then to the NCBI database. Assemblies of seven species are already in the submission portal for GenomeArk.

Impacts
What was accomplished under these goals? The workshop was held as planned and featured thirteen plenary speakers, a networking dinner, and breakout groups for collaboration planning. There were 44 in-person attendees and maximum 61 simultaneous zoom participants. The total attendance included representatives of 38 unique institutions from 19 countries. A plan to encourage collaboration versus competition in the field was developed and the attendees charged with helping spread the word. A "white paper" was developed to describe the project and submitted for considerationfollowing a pre-submission inquiry about suitability for the journal.

Publications