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Quantification of within-sample genetic heterogeneity from SNP-array data.

ABSTRACT: Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples. We created in-silico and in-vitro mixtures of tumour clones, in which diversity was known for benchmarking purposes. We found significant but highly-variable associations of our scores with diversity in-silico (p?

SUBMITTER: Martinez P

PROVIDER: S-EPMC5468233 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Quantification of within-sample genetic heterogeneity from SNP-array data.

Martinez Pierre P Kimberley Christopher C BirkBak Nicolai J NJ Marquard Andrea A Szallasi Zoltan Z Graham Trevor A TA

Scientific reports 20170612 1

Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial h ...[more]

PMID: 28607403

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