What is the difference between the ERCCs and the SIRVs?

The ERCC Spike-In Controls (ERCCs, Ambion, Thermo Fisher) allow the user to asses dynamic range, dose response, lower limit of detection, and fold-change response of RNA sequencing pipelines within the limitation of their mono-exonic, single-isoform RNA sequences. Because the ERCCs contain no transcript variants, one of the main challenges of sequencing complex transcriptomes – to identify and distinguish splice variants – cannot be evaluated using the ERCCs.

In contrast, the SIRV (Spike-In Transcript Variants) isoforms can be used to validate isoform-specific RNA sequencing workflows and to compare experiments by extrapolating the results from the well-defined isoform ground truth of a small fraction of control reads to the sample reads. Within the context of variant detection assessment of dynamic range, dose response, lower limit of detection, and fold-change response is possible as well.

The long SIRVs address the need for spike-in transcripts exceeding 2.5 kb. Their range (4 kb to 12 kb) is particularly applicable to validate long-read platforms and RNA-Seq setups.