The revolutionary technology of "Science" genome comparison

Since the first sequencing of the human genome more than 20 years ago, the study of the human genome has almost completely relied on a reference genome and comparison with other genomes to determine genetic variation

In a paper published in the journal Science on December 16, researchers at the UC Santa Cruz Genomics Institute introduced a species called Giraffe.

Corresponding author Benedict Paten is an associate professor of biomolecular engineering at the University of California, Santa Cruz and an associate director of the Institute of Genomics.

All humans have the same genes, but there are many variations in the exact sequence of the gene-this means the sequence of DNA subunits (abbreviated as A, C, T, G), and the sequence of the genome outside of protein-coding genes Most areas

The most complex variant is the structural variant, which involves rearranging large sections of code (50 or more letters)

Paten said: "The main force of genomics has always been SNVs and indels, because structural variations have been hidden from view

You can create a pan-genome reference from multiple genome sequences, and use the mathematical graph structure to represent the relationship between different sequences

The first author, Jouni Sirén, is a research scientist at the Institute of Genomics and pioneered many of Giraffe's key algorithm innovations

"This analysis method is not only better, it is as fast as current methods using linear reference genomes," said Jean Monlong, a postdoctoral researcher and co-first author at the Institute of Genomics

Inexpensive short-read sequencing is the backbone of modern genomics, and the generated sequence fragments must be mapped to a reference genome in order to be understood

Researchers found that DeepVariant, the deep learning variant caller of Google Health, uses Giraffe to compare pan-genomes and uses a single reference genome to more accurately identify SNVs and indels

Monlong said he is most excited about using pangenomics to study structural variation

He said: “Recently, many structural variations

Researchers used Giraffe to draw sequence interpretation maps from different groups of 5202 people and determined the genotypes of 167,000 recently discovered structural variations

A single reference genome must select one version of any mutation to represent, and leave other versions not to represent
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Giraffe can make genomics more inclusive by making a wider range of representative pan-genomic references practical
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Paten and others at the University of California Santa Cruz Genome Institute participated in a major effort funded by the National Human Genome Institute to establish a comprehensive human ubiquitous genome reference, which they are expected to release next year as a scientific Resources of the world
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