Disentangling sRNA-Seq

Disentangling sRNA-Seq is a bioinformatic tool to analyze small RNA sequencing data from interacting organisms, such as host-pathogen systems. The tool addresses the challenge of accurately mapping sRNA sequences to the genomes of both interacting organisms, which is difficult due to the small size of sRNAs and the presence of highly conserved regions encoding miRNAs, rRNAs, or tRNAs.

The tool employs two main strategies to disentangle sRNA-Seq data:

1. Sequence assembly (de novo and genome-guided) is used to reduce the ambiguity of mapping reads.

2. Differential expression strategies are applied to identify genuine parasite-derived sRNAs within host cells, as even confidently mapped sequences can be misleading.

The effectiveness of these methods has been validated using diverse plant and animal species known to exchange RNA with their symbionts, as well as experiments designed to study extracellular vesicle sRNAs from the parasitic nematode Heligmosomoides bakeri that enter mouse intestinal epithelial cells.