Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Nov 14;23:241. doi: 10.1186/s13059-022-02794-9

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

PMC Copyright notice

Fig. 1 — MEDICC2 algorithm. a MEDICC2 infers cancer phylogenies from SCNA data from single cells or bulk sequencing using a minimum-event distance (MED) and infers the ancestral genomes. It allows for backmutations, obeys biological constraints, and solves the phylogeny problem where ancestral genomes are not sampled. b Computing distances with WGD. Copy-number profiles are represented as vectors of positive integer copy numbers across chromosomes (here: two chromosomes with four segments each). To infer the correct MED, LOH events are considered first as lost segments cannot be re-gained by later events. WGD events span the full copy-number profile, whereas gain and loss events can affect an arbitrary number of segments within a chromosome. c Symmetric distance calculation. The MED from an ancestral state to a sample is asymmetric due to biological constraints. The final symmetric distance between two samples is computed as the sum of distances from an ancestral genome to both samples, while minimizing over all possible ancestors. d Schematic overview of the MEDICC2 workflow. Haplotype-specific copy-number profiles are either pre-phased or undergo evolutionary phasing (see e). Pairwise MEDs are computed between all genomes, followed by tree inference and ancestral reconstruction which determines the final branch lengths of the tree. Results are reported to the user as a patient summary and plot. e Evolutionary phasing. Copy-number profiles for both alleles are jointly encoded as an unweighted phasing FST P where both possible allele configurations are encoded at each position in the sequence. Evolutionary phasing then determines the optimal configuration (bold arrows) and extracts final haplotypes (orange and blue) by computing the MED between the phasing FST and two reference haplotypes. An example of major/minor copy number, phased copy number, and the MED from the diploid is shown at the bottom. Abbreviations: FST: Finite-state transducer, MED: Minimum-event distance, LOH: Loss-of-heterozygosity, WGD: Whole-genome doubling