Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

High-throughput small RNA sequencing (sRNA-seq) has facilitated many discoveries, but extracellular sRNA (ExRNA) present unique analytical challenges that are not met by current software. Therefore, we developed a novel data analysis pipeline entitled, “TIGER”, which caters to exRNA. To demonstrate the power of this tool, sRNA-seq was performed on high-density lipoproteins (HDL), apolipoprotein B particles (APOB), bile, urine, and liver samples. TIGER was able to characterize approximately 60% of lipoprotein, and >85% of liver, bile, and urine sRNA-seq depth, a significant advance compared to existing software. A key advance for the TIGER pipeline is the ability to analyze host and non-host sRNAs at genomic, parent RNA, and individual fragment levels. Results suggest that the majority of sRNAs on lipoproteins are derived from bacterial sources in the microbiome and environment. Collectively, TIGER facilitated novel discoveries of lipoprotein and biofluid sRNAs and has tremendous applicability for the field of exRNA. All samples are from matched mice, of wild-type or SRBIKO genotype: 14 HDL, 14 apoB, 14 Liver, 13 Bile, 11 Urine Please note that [1] the count.txt.tar contains multiple count files listing all annotated features (.count.txt) or fragment reads (read.count.txt) or total categorical counts (category.count.txt) for associated with a given category; [2] The DESeq2.csv.tar contains outputs from differential expression analysis using DeSeq2 comparing Wild-type vs SRBIKO; [3] The associated processed data files are indicated in the corresponding sample description field (since most of the samples were combined to generate multiple processed data).