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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

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Published on: July 5, 2019

Single-cell gene fusion detection by scFusion.

Zijie Jin¹, Wenjian Huang², Ning Shen^3,4

¹School of Mathematical Sciences, Peking University, Beijing, 100871, China.

Nature Communications

|March 1, 2022

Summary

scFusion is a new computational tool for detecting gene fusions in single-cell RNA sequencing (scRNA-seq) data. It accurately identifies fusions at the single-cell level, revealing cellular heterogeneity and transcriptional impacts.

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Area of Science:

Genomics
Computational Biology
Cancer Research

Background:

Gene fusions are critical drivers of tumor initiation and progression.
Traditional gene fusion detection relies on bulk sequencing, limiting single-cell resolution.
Single-cell RNA sequencing (scRNA-seq) presents an opportunity for single-cell fusion detection but faces challenges with noise and artifacts.

Purpose of the Study:

To develop and evaluate scFusion, a computational tool for accurate gene fusion detection in scRNA-seq data.
To assess the performance of scFusion in identifying gene fusions at the single-cell level.
To demonstrate the utility of scFusion in exploring cellular heterogeneity of gene fusions and their impact.

Main Methods:

Development of scFusion, a novel computational tool for gene fusion detection.
Performance evaluation using simulated and five real-world scRNA-seq datasets.
Application of scFusion to analyze T cell and multiple myeloma datasets.

Main Results:

scFusion demonstrates efficient and sensitive detection of gene fusions with a low false discovery rate.
The tool successfully identified invariant TCR gene recombinations in mucosal-associated invariant T cells.
scFusion detected the recurrent IgH-WHSC1 fusion in multiple myeloma, linked to WHSC1 oncogene overexpression.

Conclusions:

scFusion is a reliable tool for gene fusion detection in scRNA-seq data.
The tool enables the investigation of gene fusion heterogeneity across single cells.
scFusion facilitates the study of transcriptional consequences of gene fusions at a single-cell resolution.