DeepClone, an end-to-end protocol to study somatic mutagenesis and selection at high resolution - Repositories and figures data

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This repository contains all the code versions that were used for reporting the methods and results in the version of the linked article that has been submitted to Nature Protocols. Also uploaded to: 10.17504/protocols.io.dm6gp1jodgzp/v2 Abstract With the introduction of DNA duplex sequencing technologies, somatic mutations that occur in one or few cells in a sample can be detected. This has opened up the study of somatic evolution in scenarios that were not previously easy to access, such as normal tissues. The general adoption of DNA duplex sequencing technologies has been hindered, among other reasons, by the lack of a complete ecosystem of computational tools that support end-to-end analysis from sequencing raw data to the quantification of multiple aspects of mutagenesis and selection. Here, we present DeepClone, an end-to-end protocol to build DNA duplex sequencing libraries and to analyze the product of their sequencing, aimed at working with mammalian nuclear genomes. DeepClone includes one computational pipeline to efficiently call somatic mutations in a sample from DNA duplex sequencing reads, and a second pipeline that automates standard calculations carried out on those mutations across a cohort of samples. These include the deconvolution of the mutational processes active across samples, the estimation of positive selection on the mutations in genes, the influence of the exposure to exogenous agents on the clonal landscape of the samples, and the study of natural saturation mutagenesis across genes. DeepClone includes extensive quality control metrics associated with every step of the protocol that facilitate decision-making and critical assessment of its results. Any DNA duplex library preparation approach can be plugged to the computational pipelines, which guarantees the versatility of DeepClone to address different questions on the somatic evolution of tissues. See all acknowledgements and additional information in the linked manuscripts.

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