human reference genome

"Welcome to the era of T2T genomics,” tweeted UCSC’s Karen Miga on August 16th of this year. Then she linked to a paper on bioRxiv that begins:

"After nearly two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist.”

That would be soon fixed by Karen and her cadre of notables listed at the outset. The paper goes on to present a de novo human genome assembly that “surpasses” the GRCh38 and offers the first gapless, telomere-to-telomere assembly of a human chromosome.

Calling herself a satellite biologist, Karen has been the co-lead of the Telomere to Telomere Consortium. Her passion for quality science along with her up-to-date knowledge of the latest tools (when you google her name, the word "nanopore" often comes up beside it) make her today's torch bearer for the finest in DNA sequencing. She is the the most recent of a number of biologists and bioinformaticians to update us on the “completeness” of the human reference genome.

When will it be finished? What does finished mean? How far does this latest phase get us? And who is paying attention?

Storylines repeat in genome science every decade or so. The human genome is complete. No. Now it's complete. Or, in the 90's, it was first announced that the first chromosome was sequenced. We have the same story for you today--breaking news from a paper that has not even been published yet: the first “complete” assembly of a human chromosome, end to end, telomere to telomere.

So what’s going on?

As every bioinformatician will tell you: There are levels of completeness. It is these levels of completeness that have kept folks busy at the NHGRI for many years and will for years to come. For in some of the incomplete areas, the "holes", lurk compelling secrets.

“These genome assemblies come out of very complex software, and they often contain numerous errors. And so it's key to go back into the wet lab and validate in any way that we can that our reconstruction is accurate."

That’s today’s guest, Adam Phillippy, who has been at the forefront of bioinformatics for over a decade at the NHGRI and has been an important contributor to the problems of genome assembly. He is the head of the Genome Informatics Section, which he founded.

We jumped at the chance to talk to Adam about his upcoming paper on the now complete X chromosome and the chance to hear his thoughts on the “completeness” of the human reference genome. Adam goes on to tell us that the energy at NHGRI is now shifting toward the Human Pan Genome, an attempt to represent all variations of humanity into the reference genome.

What are the challenges for such a project? And hey Adam, while we have you on, please give us your thoughts on sequencing technologies in 2019 as only a bioinformatician can.