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NOMAD2 provides ultra-efficient, scalable, and unsupervised discovery on raw sequencing reads

Kokot, M.; Dehghannasiri, R.; Baharav, T. Z.; Salzman, J.; Deorowicz, S.

2023-03-21 bioinformatics
10.1101/2023.03.17.533189 bioRxiv
Show abstract

SPLASH is an unsupervised, reference-free, and unifying algorithm that discovers regulated sequence variation through statistical analysis of k-mer composition, subsuming many application-specific methods. Here, we introduce SPLASH2, a fast, scalable implementation of SPLASH based on an efficient k-mer counting approach. SPLASH2 enables rapid analysis of massive datasets from a wide range of sequencing technologies and biological contexts, delivering unparalleled scale and speed. The SPLASH2 algorithm unveils new biology (without tuning) in single-cell RNA-sequencing data from human muscle cells, as well as bulk RNA-seq from the entire Cancer Cell Line Encyclopedia (CCLE), including substantial unannotated alternative splicing in cancer transcriptome. The same untuned SPLASH2 algorithm recovers the BCR-ABL gene fusion, and detects circRNA sensitively and specifically, underscoring SPLASH2s unmatched precision and scalability across diverse RNA-seq detection tasks.

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