Reference Genome Choice Can Skew Genomics Study Results

Biomarker Technologies (BMKGene) has published insights into the critical role of reference genome selection in genomics research. When analyzing DNA or RNA sequencing data, reads are typically mapped to a reference genome. However, this process can introduce biases if the chosen reference genome does not adequately represent the genetic diversity of the study organism.

A reference genome usually represents a single individual or a limited set of genomes, failing to capture the full genetic spectrum within a species. This can lead to "reference genome bias," where reads from a study sample that differ from the reference may be difficult or impossible to map accurately. This can result in the loss of valuable genetic information or lead to inaccurate conclusions.

Reference genome bias can significantly affect various genomics applications. In DNA sequencing, it can skew variant detection and population genetics analyses, particularly when studying wild populations or genetically diverse species. For RNA sequencing (RNA-seq), this bias can lead to inaccurate gene expression level measurements, impacting studies on hybrids or interspecies comparisons.

Biomarker Technologies advises that the impact of reference genome bias can be minimized by choosing the most representative and high-quality reference genome available. Ideally, the reference genome should be from the same species and as complete as possible, preferably a full genome generated using modern long-read sequencing technologies.