Novel Functional Sequences Uncovered through a Bovine Multiassembly Graph
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Abstract
Abstract Linear reference genomes are typically assembled from single individuals. They are unable to reflect the genetic diversity of populations and lack millions of bases. To overcome such limitations and make non-reference sequences amenable to genetic investigations, we build a multi-assembly graph from six reference-quality assemblies from taurine cattle and their close relatives. We uncover 70,329,827 bases that are missing in the bovine linear reference genome. The missing sequences encode novel transcripts that are differentially expressed between individual animals. Reads which were previously poorly or unmapped against the bovine reference genome now align accurately to the non-reference sequences. We show that the non-reference sequences contain polymorphic sites that segregate within and between breeds of cattle. Our efforts to uncover novel functional sequences from a multi-assembly graph pave the way towards the transition to a more representative bovine reference genome.
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Graph pangenomes represent genomes as network structures, allowing for the simultaneous storage of multiple haplotypes and complex nested variations.
“Unlike linear concatenations, graph pangenomes represent genomes as network structures (nodes and edges), allowing for the simultaneous storage of multiple haplotypes and complex nested variations [183,184].”
From The Genomic Landscape of Cattle: Domestication, Dispersal, and Adaptive Evolution (2026) · cites this paper as [184]
The graph-construction passages describe nodes and edges traversed by different assembly paths, and the structural-variation section reports multiple alleles within graph bubbles. That supports representing multiple genome sequences and variants in one graph. The Discussion says this implementation contains only insertions and deletions and cannot accurately integrate inversions or translocations; our copy does not establish the claimed capacity for complex nested variations. (LLM, conf=0.87)
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- Authors
- Crysnanto, D., Leonard, A. S., Fang, Z.-H., & Pausch, H.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Crysnanto, Danang
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-05-10
- Volume
- 118
- Issue
- 20
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8157972
- OpenAlex
- W3162276363
- Cited by
- 96
- References
- 75
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 26 · 2023: 22 · 2022: 15 · 2021: 5
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_185229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- pan-genome, cattle, novel genes, differentially expressed genes, polymorphic sites, genomic variation
- MeSH terms
- Whole Genome Sequencing, Animals, Cattle, Female, Male
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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