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Methods {#Sec9}
=======

miRNA-seq data {#Sec10}
————–

We downloaded publicly available miRNA-seq data from peripheral blood samples of SMC patients, healthy donors and their age-matched controls from GEO: GSE77370 and GSE100895 \[[@CR9], [@CR21]\]. GSE77370 contains small RNA sequences from both blood and bone marrow of three SMC patients, two healthy donors and four age-matched controls. GSE100895 contains small RNA sequences from blood of 8 SMC patients and three age-matched controls.

Identification of known and novel miRNAs in small RNA sequence data {#Sec11}
——————————————————————-

The small RNA sequences were first aligned to the human reference genome (version hg38) using Bowtie2 \[[@CR23]\]. Identical reads were collapsed into one read by keeping the more-frequent read. Unique reads were aligned to the human genome using Bowtie \[[@CR24]\] allowing three mismatches. Sequences that aligned to known human miRNAs in miRBase (version 21) were considered as known miRNAs, and those that did not align were considered as novel miRNAs. A unique read was defined as a sRNA sequenced at least once in at least one of the samples.

Identification of known and novel miRNA prediction regions {#Sec12}
———————————————————-

All known and novel miRNA regions were obtained by applying miRDeep2 \[[@CR25]\] with default parameters to align the overlapping reads to the hg38 genome.

Enrichment analysis of predicted miRNAs {#Sec13}
—————————————

We obtained genes predicted to be targeted by individual miRNAs using TargetScan v7.1 \[[@
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