Pan Genome Research Tool Kit (PGR-TK) for T2T F2F meeting

A summary about Pan Genome Research Tool Kit can help for human pan gnome analysis.

Transcript

1. PGR-TK Pangenome & T2T Analysis T2T F2F meeting, UCSC, Aug, 2022 Jason Chin
2. How does (internet powered) “AI” Interpret Pangenome?
3. Domen Jemec
4. Pan Genomics Research Tool Kit (PGR-TK) • A non-”AI” approach though :p • Promote T2T and pangenome resources for diagnostics / testing applications in my organization (GeneDX + Sema4) Code: https://github.com/Sema4-Research/pgr-tk Document: https://sema4-research.github.io/pgr-tk/ Example: https://github.com/sema4-Research/pgr-tk-notebooks preprint: Multiscale Analysis of Pangenome Enables Improved Representation of Genomic Diversity For Repetitive And Clinical Relevant Genes | bioRxiv (https://www.biorxiv.org/content/10.1101/2022.08.05.502980v)
5. Minimizer Anchored Pangenomics Graph a:b a:c c:h h:e h:i i:f b:c c:d d:e e:f f:g c h i f h e f g e f b c d e a c h i c d b a a a a a a b b b c c c c d d h h e e e i f f f f g g e f g g g Sequence with minimizer anchors Graph Vertex: A set of sequences with shared minimizer anchors at both ends Induced Minimizer Anchored Pan-genomics Graph
6. Pangenomics Graph at Multi- scales w=128, k=32, r =8 12.5 kbp 12.5 kbp 12.5 kbp w=128, k=32, r =6 w=128, k=32, r =4 (w, k, r) = (48, 56, 12) (w, k, r) = (48, 56, 4) KCNE1 AMY1A
7. Principal Bundle Decomposition
8. DAZ 1/2/3/4 System 175 kbp DAZ3 DAZ4 DAZ1 DAZ2 GRCh38 GRCh38 HG002 HG002
9. DAZ 1/2/3/4 System
10. DAZ 1/2/3/4 Principal Bundle MAP Graph
12. Whole ChrY euchromatin MAP graph and principal bundle decomposition (28Mb region with HPRC assemblies) 28 Mbp
13. TSPY1 Repeat Analysis
14. MAP Graph For The Whole TSPY1 Region the repeat
15. Break The Sequences Into Repeat Units • Identify high multiplicity principal bundles • Pick the ”most repetitive but non- trivial principal bundle”, identify the locations where a sequence start to overlaps with the bundle as the starting points of the repeat elements. • Maybe more sophisticate HMM can be deployed in the future the repeat
16. Principal Bundle Decomposition of the TSPY repeat unit
17. PCA Analysis of The Repeat Units (TSPY) 400+ repeat units Binary Vector by projecting the repeats to the principal bundles
18. Not Just TSPY1 HLA Class 2 loci (not tandem repeat though) LPA KIV2 repeat KANTL2
19. Three major (or five?) subgroups of the KIV-II repeat in LPA
20. We need better tools together to "cook" pangenome!! Acknowledge: Sairam Behera, Asif Khalak, Fritz Sedlazeck, Justin Wagner, Justin M. Zook for great collaborations and T2T / HPRC for data generation & release