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by claude@2026-06, 2026-06-24
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The paper addresses how linear reference genomes create reference bias that skews read mapping and variant discovery, and it proposes a user-friendly solution for exploring pangenome graphs. It introduces PangyPlot, a genome browser that keeps linear-style navigation while integrating gene annotations and using a dynamic physics-based layout to abstract complex variation into interpretable views. The authors built and visualized a chromosome 7 pangenome graph from 101 individuals with cystic fibrosis and then used PangyPlot alongside graph-based analysis to fine-map a repeat-dense modifier locus on chromosome 5, identifying a repeat expansion in the 5′ end of EXOC3, with an explicitly demonstrated capability to display base-level and large structural variation. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Linear reference genomes have standardized genomics research but remain limited by reference bias, which skews read mapping and variant discovery. This bias can distort the interpretation of genetic variation, particularly for populations that are genetically distant from the reference. Pangenome graphs, such as those generated by the Human Pangenome Reference Consortium (HPRC), mitigate this limitation by integrating diverse haplotypes into a unified representation of human genetic variation. However, the complexity of graph-based data and the lack of intuitive visualization tools have hindered broader adoption. Here we introduce PangyPlot , a genome browser that simplifies exploration of pangenome graphs by retaining linear-style navigation, integrating gene annotations, abstracting complex variation into interpretable structures, and employing a dynamic, physics-based layout optimization engine. We demonstrate its utility by constructing a chromosome 7 graph from 101 individuals with cystic fibrosis (CF), capturing a broad spectrum of genetic variation. Using PangyPlot , we visualized CF-relevant loci and compared results with existing graph viewers, highlighting its ability to display both base-level and large structural variation. With an additional 64 PacBio HiFi assemblies, we fine-mapped a repeat-dense CF modifier locus on chromosome 5, where PangyPlot was used in conjunction with graph-based analysis to identify a repeat expansion in the 5 ′ end of EXOC3 that may promote G-quadruplex formation and affect gene expression. Together, these examples demonstrate PangyPlot ‘s capacity to make populationlevel variation interpretable. To support broader use of graph-based resources, we also released a live public instance of PangyPlot preloaded with HPRC data ( https://pangyplot.research.sickkids.ca/ ).
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Abstract
Linear reference genomes have standardized genomics research but remain limited by reference bias, which skews read mapping and variant discovery. This bias can distort the interpretation of genetic variation, particularly for populations that are genetically distant from the reference. Pangenome graphs, such as those generated by the Human Pangenome Reference Consortium (HPRC), mitigate this limitation by integrating diverse haplotypes into a unified representation of human genetic variation. However, the complexity of graph-based data and the lack of intuitive visualization tools have hindered broader adoption.
Here we introduce PangyPlot, a genome browser that simplifies exploration of pangenome graphs by retaining linear-style navigation, integrating gene annotations, abstracting complex variation into interpretable structures, and employing a dynamic, physics-based layout optimization engine. We demonstrate its utility by constructing a chromosome 7 graph from 101 individuals with cystic fibrosis (CF), capturing a broad spectrum of genetic variation. Using PangyPlot, we visualized CF-relevant loci and compared results with existing graph viewers, highlighting its ability to display both base-level and large structural variation. With an additional 64 PacBio HiFi assemblies, we fine-mapped a repeat-dense CF modifier locus on chromosome 5, where PangyPlot was used in conjunction with graph-based analysis to identify a repeat expansion in the 5′ end of EXOC3 that may promote G-quadruplex formation and affect gene expression. Together, these examples demonstrate PangyPlot ‘s capacity to make populationlevel variation interpretable. To support broader use of graph-based resources, we also released a live public instance of PangyPlot preloaded with HPRC data (https://pangyplot.research.sickkids.ca/).
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵** A list of authors and their affiliations appears at the end of the paper.
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