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Related Concept Videos

Next-generation Sequencing03:00

Next-generation Sequencing

The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

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A practical guide to cancer subclonal reconstruction from DNA sequencing.

Maxime Tarabichi1,2, Adriana Salcedo3,4,5,6,7, Amit G Deshwar8

  • 1The Francis Crick Institute, London, UK.

Nature Methods
|January 5, 2021
PubMed
Summary

Subclonal reconstruction from DNA sequencing reveals cancer evolution. This guide outlines computational methods, assumptions, and best practices for analyzing tumor samples to understand mutation ordering and processes.

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Area of Science:

  • Oncology
  • Computational Biology
  • Genomics

Background:

  • Subclonal reconstruction from bulk tumor DNA sequencing is crucial for understanding cancer evolution.
  • It provides insights into mutation clonality and the order of genetic alterations.
  • Analyzing mutational processes within tumors requires advanced computational techniques.

Purpose of the Study:

  • To outline complex computational approaches for subclonal reconstruction.
  • To identify assumptions and uncertainties inherent in these methods.
  • To suggest best practices for analysis and quality assessment in cancer evolution studies.

Main Methods:

  • Review of computational strategies for subclonal reconstruction using single and multiple tumor samples.
  • Identification of key steps, assumptions, and potential sources of error in the analysis pipeline.
  • Development of guidelines for robust data analysis and quality control.

Main Results:

  • A comprehensive overview of subclonal reconstruction methodologies.
  • Detailed examination of the assumptions and uncertainties associated with each analytical step.
  • Recommendations for best practices in data analysis and quality assessment.

Conclusions:

  • Subclonal reconstruction is a vital tool for studying cancer evolution.
  • Understanding computational methods, assumptions, and uncertainties is essential for accurate analysis.
  • This guide serves as a practical resource for researchers utilizing these techniques.