CONIPHER: a computational framework for scalable phylogenetic reconstruction with error correction.


Journal

Nature protocols
ISSN: 1750-2799
Titre abrégé: Nat Protoc
Pays: England
ID NLM: 101284307

Informations de publication

Date de publication:
28 Nov 2023
Historique:
received: 11 01 2023
accepted: 24 08 2023
medline: 29 11 2023
pubmed: 29 11 2023
entrez: 28 11 2023
Statut: aheadofprint

Résumé

Intratumor heterogeneity provides the fuel for the evolution and selection of subclonal tumor cell populations. However, accurate inference of tumor subclonal architecture and reconstruction of tumor evolutionary histories from bulk DNA sequencing data remains challenging. Frequently, sequencing and alignment artifacts are not fully filtered out from cancer somatic mutations, and errors in the identification of copy number alterations or complex evolutionary events (e.g., mutation losses) affect the estimated cellular prevalence of mutations. Together, such errors propagate into the analysis of mutation clustering and phylogenetic reconstruction. In this Protocol, we present a new computational framework, CONIPHER (COrrecting Noise In PHylogenetic Evaluation and Reconstruction), that accurately infers subclonal structure and phylogenetic relationships from multisample tumor sequencing, accounting for both copy number alterations and mutation errors. CONIPHER has been used to reconstruct subclonal architecture and tumor phylogeny from multisample tumors with high-depth whole-exome sequencing from the TRACERx421 dataset, as well as matched primary-metastatic cases. CONIPHER outperforms similar methods on simulated datasets, and in particular scales to a large number of tumor samples and clones, while completing in under 1.5 h on average. CONIPHER enables automated phylogenetic analysis that can be effectively applied to large sequencing datasets generated with different technologies. CONIPHER can be run with a basic knowledge of bioinformatics and R and bash scripting languages.

Identifiants

pubmed: 38017136
doi: 10.1038/s41596-023-00913-9
pii: 10.1038/s41596-023-00913-9
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
ID : CC2041
Pays : United Kingdom

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Kristiana Grigoriadis (K)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.

Ariana Huebner (A)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.

Abigail Bunkum (A)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Metastasis Lab, University College London Cancer Institute, London, UK.
Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK.

Emma Colliver (E)

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Alexander M Frankell (AM)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Mark S Hill (MS)

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Kerstin Thol (K)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.

Nicolai J Birkbak (NJ)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.

Charles Swanton (C)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. charles.swanton@crick.ac.uk.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. charles.swanton@crick.ac.uk.
Department of Oncology, University College London Hospitals, London, UK. charles.swanton@crick.ac.uk.

Simone Zaccaria (S)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. s.zaccaria@ucl.ac.uk.
Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK. s.zaccaria@ucl.ac.uk.

Nicholas McGranahan (N)

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. nicholas.mcgranahan.10@ucl.ac.uk.
Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. nicholas.mcgranahan.10@ucl.ac.uk.

Classifications MeSH