Whole exome sequencing in molecular diagnostics of cancer decreases over time: evidence from a cost analysis in the French setting

Bayle, Arnaud; Droin, Nathalie; Besse, Benjamin; Zou, Zhaomin; Boursin, Yannick; Rissel, S.; Solary, Éric; Lacroix, Ludovic; Rouleau, Étienne; Borget, Isabelle; Bonastre, Julia

doi:10.1007/s10198-021-01293-1

Cited by 12 publications

(8 citation statements)

References 45 publications

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“…This observation can be explained thereby that the experimental populations are RIL populations, while the model underlying the nPGM approach was established based on simulated F2 populations. The total number of recombination events accumulated in the gametes of a RIL, after endless selfing generations, was about twice the number of such events in an F2 population [ 43 ]. Therefore, if the absolute value of the map positions is of interest, then the model underlying nPGM approach needs to be derived de novo for the population type under consideration.…”

Section: Discussionmentioning

confidence: 99%

“…One possibility would be to consider this aspect in our simulations of genotyping with an SNP array. However, with today’s sequencing costs [ 43 ], applying our method to datasets created from the sequencing of pooled samples is even more economically attractive. Therefore, we estimated the accuracy of recombination rate estimation from simulated pool sequencing samples.…”

Section: Discussionmentioning

confidence: 99%

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Accurate recombination estimation from pooled genotyping and sequencing: a case study on barley

2022

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Sexual reproduction involves meiotic recombination and the creation of crossing over between homologous chromosomes, which leads to new allele combinations. We present a new approach that uses the allele frequency differences and the physical distance of neighboring polymorphisms to estimate the recombination rate from pool genotyping or sequencing. This allows a considerable cost reduction compared to conventional mapping based on genotyping or sequencing data of single individuals. We evaluated the approach based on computer simulations at various genotyping depths and population sizes as well as applied it to experimental data of 45 barley populations, comprising 4182 RIL. High correlations between the recombination rates from this new pool genetic mapping approach and conventional mapping in simulated and experimental barley populations were observed. The proposed method therefore provides a reliable genetic map position and recombination rate estimation in defined genomic windows.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accurate recombination estimation from pooled genotyping and sequencing: a case study on barley

2022

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“…However, TMB quantification based on the panel assay is still subject to fluctuation (Figure 3B), which may impact clinical decisions, and thus, comprehensive sequencing methods including WES are considered optimal for reproducible and reliable measurements 35 . As the cost of WES decreases and efforts toward the implementation of WES as a routine cancer treatment continue to advance 36,37 , the combination of precision-improved TMB calculation and the orthogonal GS-PRACTICE method will usher in precise patient selection for ICI treatment.…”

Section: Discussionmentioning

confidence: 99%

Mutation burden-orthogonal tumor genomic subtypes delineate responses to immune checkpoint therapy

Takamatsu

Hamanishi

Brown

et al. 2021

Preprint

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Background: In cancer therapy, precise tumor-agnostic biomarkers that predict response to immune checkpoint inhibitors (ICIs) are needed. To explain treatment response differences among tumor types, the application of mutational signatures, patterns of genomic alterations that reflect differences in distinct underlying carcinogenic processes, holds promise but has not been extensively integrated into prediction methodologies. Methods: Based on mutational signature analysis, we developed a stratification for all solid tumors in The Cancer Genome Atlas (TCGA). Then, we developed the Tumor Genomic Subtype Analyzer (TGSA) to classify tumors submitted to whole-exome sequencing. Using existing data from 938 pan-cancer ICI-treated cases with outcomes, we evaluated the subtype-response predictive performance. Results: Systematic analysis on TCGA samples identified eight tumor genomic subtypes, which were characterized by features represented by smoking exposure, ultraviolet light exposure, APOBEC enzyme activity, POLE mutation, mismatch repair deficiency, homologous recombination deficiency, genomic stability, and aging. The former five subtypes were presumed to form an immune-responsive group acting as candidates for ICI therapy because of their high expression of immune-related genes and enrichment in cancer types with FDA approval for ICI monotherapy. In the validation cohort, the samples assigned by TGSA to the immune-reactive subtypes were significantly related to ICI response independent of cancer type and high TMB status. Conclusion: Mutational signature-based tumor subtyping can serve as a tumor-agnostic biomarker for ICI response prediction. The results indicate that the mutational process underlying carcinogenesis affects tumor immunogenicity, and thus sensitivity to ICI.

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“…1 SNPversity only accepts HDF5 files as input for variant matrices, for genome annotations it accepts GFF3 files as input. 2 SNPversity does not provide a dedicated track for genome annotations or features but it can display IDs of genes as text labels if a variant is located within the bounds of a gene. 3 SNPversity offers export as VCF files, but at the time of the test this function did not work and a "Proxy Error" message from the webserver occurred.…”

Section: Comparison With Existing Toolsmentioning

confidence: 99%

“…In times of ever-increasing quantity and quality of sequencing data that is driven by the ongoing reduction of sequencing costs and simultaneously increasing computing power, an everincreasing amount of data of genomic diversity is being generated, which is almost impossible to keep track of in its entirety [1,2]. Rather, there is a need to reduce complexity through models that aggregate the data in a meaningful way but preserve the information capacity.…”

Section: Introductionmentioning

confidence: 99%

DivBrowse – interactive visualization and exploratory data analysis of variant call matrices

König

Beier

Mascher

et al. 2022

Preprint

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Background: The sequencing of whole genomes is becoming increasingly affordable. In this context large-scale sequencing projects are generating ever larger datasets of species-specific genomic diversity. As a consequence, more and more genomic data needs to be made easily accessible and analyzable to the scientific community. Results: We present DivBrowse, a web application for interactive visualization and exploratory analysis of genomic diversity data stored in Variant Call Format (VCF) files of any size. By seamlessly combining BLAST as an entry point together with interactive data analysis features such as principal component analysis in one graphical user interface, DivBrowse provides a novel and unique set of exploratory data analysis capabilities for genomic biodiversity datasets. The capability to integrate DivBrowse into existing web applications supports interoperability between different web applications. Built-in interactive computation of principal component analysis allows users to perform ad-hoc analysis of the population structure based on specific genetic elements such as genes and exons. Data interoperability is supported by the ability to export genomic diversity data in VCF and General Feature Format (GFF3) files. Conclusion: DivBrowse offers a novel approach for interactive visualization and analysis of genomic diversity data and optionally also gene annotation data by including features like interactive calculation of variant frequencies and principal component analysis. The use of established standard file formats for data input supports interoperability and seamless deployment of application instances based on the data output of established bioinformatics pipelines.

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Whole exome sequencing in molecular diagnostics of cancer decreases over time: evidence from a cost analysis in the French setting

Cited by 12 publications

References 45 publications

Accurate recombination estimation from pooled genotyping and sequencing: a case study on barley

Accurate recombination estimation from pooled genotyping and sequencing: a case study on barley

Mutation burden-orthogonal tumor genomic subtypes delineate responses to immune checkpoint therapy

DivBrowse – interactive visualization and exploratory data analysis of variant call matrices

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