Methods and applications of gene fusion detection in cell-free DNA analysis

Abstract

Systems and methods are disclosed for determining gene fusion by determining a fused read containing sequencing data of a portion of a fused chromosome DNA molecule; determining a predetermined point on the genome with least one mapped portion of the fused read clipped at the predetermined point (a breakpoint); identifying two mapped read portions from two breakpoints (breakpoint pair) as a potential fusion candidate; creating one or more fusion sets based on breakpoint pairs and clustering the fusion sets into one or more fusion clusters; and identifying each fusion cluster meeting a predetermined criterion as a gene fusion.

Description

CROSS-REFERENCE[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 239,879, filed Oct. 10, 2015, which application is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Cancerous cells may have chromosomes that are fused together. If such a chromosome is sequenced, it will generate reads that can be mapped into two different zones (on the same or different chromosomes) of the genome. Gene fusion plays a role in the evolution of gene architecture. Duplication, sequence divergence, and recombination are the major contributors at work in gene evolution. When gene fusion happens in non-coding sequence region, it can lead to the misregulation of the expression of a gene now under the control of the cis-regulatory sequence of another gene. If it happens in coding sequences, gene fusion can cause the assembly of a new gene, allowing the appearance of new functions by adding peptide modules into a multi domain protein.[0003]Chromos...

AI Technical Summary

Benefits of technology

The patent describes a method and system for analyzing genetic information by identifying fused reads containing sequencing data of a portion of a fused chromosome DNA molecule. The method involves determining a fused read by clipping the read at a breakpoint on the genome, identifying two mapped read portions from the breakpoint as a potential fusion candidate, creating fusion sets based on the breakpoint pairs, and identifying each fusion cluster as a gene fusion if it meets certain criteria. The system includes a DNA sequencer and a processor for running computer code to process genetic sequence read data. The technical effect of this patent is to provide a reliable and accurate method for identifying gene fusions, which can help in the diagnosis and treatment of genetic disorders.

Problems solved by technology

When gene fusion happens in non-coding sequence region, it can lead to the misregulation of the expression of a gene now under the control of the cis-regulatory sequence of another gene.

Recent developments such as high-throughput sequencing and custom DNA microarrays bear promise of introduction of more efficient methods, but are still inadequate.

Images