Researchers build near-complete genome map of J. Craig Venter using simpler workflow

Scientists at SickKids and the J. Craig Venter Institute have used long-read sequencing to assemble HuRef2.0, a near-complete version of Venter’s personal genome. The work shows a lower-cost path to high-quality personal genome assemblies that could be more practical in clinical and research settings.

Why it matters: - The HuRef2.0 assembly shows a simpler route to near-complete personal genomes, which could make detailed genome reconstruction more scalable in research and clinical settings. - The workflow approaches a long-sought goal of a complete genome for about $1,000, according to Stephen Scherer, chief of research at SickKids. - More complete personal genomes can help researchers see medically relevant DNA changes in their full chromosomal context instead of as isolated variants.

What happened: - Researchers led by The Centre for Applied Genomics at The Hospital for Sick Children in Toronto produced a near-complete reconstruction of J. Craig Venter’s genome called HuRef2.0. - The study was published in the Proceedings of the National Academy of Sciences. - J. Craig Venter Institute founder J. Craig Venter was a co-author on the paper. - The team used Oxford Nanopore long-read sequencing to build the assembly from standard high-quality blood DNA. - The project builds on a collaboration between JCVI and SickKids that began with the original HuRef genome in 2007.

The details: - Human genomes contain two inherited sets of chromosomes, one from each parent. - Most sequencing compares a person’s DNA against a reference genome, while personal genome reconstruction tries to piece together the person’s actual chromosomes. - HuRef2.0 reaches much closer to telomere-to-telomere reconstruction, with 24 gapless chromosome sequences covering all of Venter’s chromosomes, including the X and Y sex chromosomes. - The assembly is highly accurate, but it is not yet a fully resolved reconstruction of both inherited chromosome sets. - Some highly repetitive regions remain difficult to assemble reliably. - The team did not use the specially prepared extra-long DNA and combined sequencing-plus-mapping methods often used for telomere-to-telomere assemblies. - The original HuRef genome in 2007 was the first published genome assembly of one individual to account for both inherited chromosome sets, or a diploid genome. - The 2007 work removed other donors’ DNA contributions from the earlier draft and added new data using the sequencing technology available then. - HuRef revealed that larger DNA changes, including added, missing, repeated and rearranged stretches, contribute more to human genetic variation than scientists had previously recognized. - The original HuRef contained more than 30,000 separate DNA pieces. - The initial HuRef2.0 assembly reduced that to 26 pieces. - Closing two remaining gaps produced sequences spanning all of Venter’s chromosomes. - The new assembly enabled researchers to identify much longer stretches of DNA belonging to the same inherited chromosome copy, an improvement of more than 20-fold over the original HuRef. - The team examined a complex immune-related region, parts of the Y chromosome and a region of chromosome 22 where missing or extra DNA can cause disease. - Different analysis methods revealed different genetic changes, and no single method found every potentially medically relevant difference.

Between the lines: - The paper highlights a shift from reference-based sequencing toward direct reconstruction of a person’s chromosomes, which could improve how scientists interpret disease-related variants. - The work also underscores a practical tradeoff: better continuity and accuracy are now possible with simpler inputs, but some repetitive regions and full diploid reconstruction remain unresolved. - Venter’s genome offers a rare side-by-side view of sequencing progress across three eras: the 2001 draft human genome, the 2007 HuRef assembly and now HuRef2.0. - The study is among the final scientific papers co-authored by Venter, who died April 29, 2026.

What’s next: - The team says the findings support continued work to reconstruct both inherited chromosome copies more completely and compare personal genomes directly. - The approach may be useful for larger studies that need high-quality genome assemblies at lower cost. - Related work is continuing through efforts to combine phased diploid genome sequencing with medical imaging, clinical data and computer analysis. - The paper, “The revised diploid genome sequence of an individual human: A workflow for near telomere-to-telomere assemblies using only Oxford Nanopore Technologies Simplex-reads,” is available in PNAS.

The bottom line: - HuRef2.0 shows that near-complete personal genomes may be achievable with a more practical workflow, bringing personalized genomic medicine a step closer to broader use.