A pangenome reference overcomes the inherent limitation of any individual reference genome by integrating the variation present in a population. We present the Human Pangenome Reference Consortium’s (HPRC) Release 2 (HPRC2), an openly available, second phase pangenome that is an approximately fivefold expansion in genome number over HPRC Release 1 (HPRC1) and measurable improvement in genome completeness, contiguity, and accuracy. Selecting samples with a principled algorithm prioritising common variant coverage, HPRC2 contributes 460 haplotypes that together capture over 99% of common variation observed in the All of Us Research Program v8 cohort. Combining high-coverage long and ultra-long reads with modern assemblers and polishers, we produce thousands of telomere-to-telomere (T2T) chromosomes, and relative to HPRC1 halve the number of structurally unreliable regions as well as individual base errors per haplotype. We complement the assemblies with whole genome multiple alignments and gene annotations, and derive formal pangenome coordinate systems for addressing off-reference variation, demonstrating that individual human genomes contain more than one hundred thousand variants not succinctly described with respect to existing reference genomes. We also present the first matched long-read backed pantranscriptome and panepigenome at this scale, provide continuous local-ancestry estimates spanning every genome, and outline a host of new tools and applications that leverage the pangenome resource for improved genomics analysis.
Julian K. Lucas, Prajna Hebbar, Wen-Wei Liao et al.· bioRxiv· 1 citation
A vertex-reinforced random walk steps to a neighbour with probability proportional to $1+\beta n^{a}$, where $n$ counts previous visits to that neighbour and $a\in(0,1)$ sets the memory strength. On the rooted $b$-ary tree the exponential growth of the vertex set drives the walk outward while the reinforcement pulls it back. We report a sharp condensation transition of the occupation measure at a finite $\beta_c(a,b)$: below it the occupation spreads and the range grows linearly; above it a single vertex holds an $O(1)$ fraction of the time, stable in the observation time, while the range keeps growing very slowly, at a rate better described by $\log t$ than by any power. We do not find the range to be bounded, and keep this condensation distinct from finite-range localization. Four estimators locate the same threshold, which shows no systematic drift out to $t=3\times10^{7}$. In a frozen environment the walk is reversible, with edge conductances $c_{uv}=w_{u}w_{v}$, $w_{v}=1+\beta n_{v}^{a}$, and measure $\mu_{v}\propto w_{v}\sum_{u\sim v}w_{u}$ describing the condensed core, whose neighbour coupling we test directly. Reversibility places the escape at the frontier within the branching-number criterion for biased walks on trees, predicting $\beta_c\propto b-1$; the measured lines for $b=2,3,4$ collapse under division by $b-1$ to a few percent (bootstrap). The value $a=1/2$ that governs the walk on $\mathbb{Z}$ enters only as the marginal exponent of the condensed profile. Near $\beta_c$ the occupancy is non-self-averaging and bimodal, a coexistence-type phenomenology.
Bonhwang Koo, Edward Ju· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
