Reference-free discovery with barcoded single-cell sequencing

Roozbeh Dehghannasiri; Marek Kokot; Alexander L. Starr; Jamie Maziarz; Tal Gordon; Serena Y. Tan; Peter L. Wang; Ayelet Voskoboynik; Jacob M. Musser; Sebastian Deorowicz; Julia Salzman

doi:10.1038/s41587-026-03084-6

Reference-free discovery with barcoded single-cell sequencing

Roozbeh Dehghannasiri
, Marek Kokot
, Alexander L. Starr
, Jamie Maziarz
, Tal Gordon
, Serena Y. Tan
, Peter L. Wang
, Ayelet Voskoboynik
, Jacob M. Musser
, Sebastian Deorowicz
, Julia Salzman

Department of Algorithmics and Software (RAU/RAU5)

Stanford University
Yale University

Research output: Contribution to journal › Article › peer-review

Abstract

Single-cell RNA sequencing (scRNA-seq) analyses typically focus on alignment and differential gene expression, being blind to other transcriptome variation. Here we present sc-SPLASH for statistics-first, reference-free discovery on barcoded scRNA-seq and spatial transcriptomics; its independent BKC submodule optimizes barcoded data preprocessing and is approximately 50-fold faster than UMI-tools. sc-SPLASH discovers secreted repeat proteins in immune-like cells of sponge (Spongilla; missing from the reference) and tunicate (Ciona).

Original language	English
Journal	Nature Biotechnology
DOIs	https://doi.org/10.1038/s41587-026-03084-6
Publication status	Accepted/In press - 2026

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Biomedical Engineering
Molecular Medicine

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10.1038/s41587-026-03084-6

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title = "Reference-free discovery with barcoded single-cell sequencing",

abstract = "Single-cell RNA sequencing (scRNA-seq) analyses typically focus on alignment and differential gene expression, being blind to other transcriptome variation. Here we present sc-SPLASH for statistics-first, reference-free discovery on barcoded scRNA-seq and spatial transcriptomics; its independent BKC submodule optimizes barcoded data preprocessing and is approximately 50-fold faster than UMI-tools. sc-SPLASH discovers secreted repeat proteins in immune-like cells of sponge (Spongilla; missing from the reference) and tunicate (Ciona).",

author = "Roozbeh Dehghannasiri and Marek Kokot and Starr, \{Alexander L.\} and Jamie Maziarz and Tal Gordon and Tan, \{Serena Y.\} and Wang, \{Peter L.\} and Ayelet Voskoboynik and Musser, \{Jacob M.\} and Sebastian Deorowicz and Julia Salzman",

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doi = "10.1038/s41587-026-03084-6",

language = "English",

journal = "Nature Biotechnology",

issn = "1087-0156",

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T1 - Reference-free discovery with barcoded single-cell sequencing

AU - Dehghannasiri, Roozbeh

AU - Kokot, Marek

AU - Starr, Alexander L.

AU - Maziarz, Jamie

AU - Gordon, Tal

AU - Tan, Serena Y.

AU - Wang, Peter L.

AU - Voskoboynik, Ayelet

AU - Musser, Jacob M.

AU - Deorowicz, Sebastian

AU - Salzman, Julia

PY - 2026

Y1 - 2026

N2 - Single-cell RNA sequencing (scRNA-seq) analyses typically focus on alignment and differential gene expression, being blind to other transcriptome variation. Here we present sc-SPLASH for statistics-first, reference-free discovery on barcoded scRNA-seq and spatial transcriptomics; its independent BKC submodule optimizes barcoded data preprocessing and is approximately 50-fold faster than UMI-tools. sc-SPLASH discovers secreted repeat proteins in immune-like cells of sponge (Spongilla; missing from the reference) and tunicate (Ciona).

AB - Single-cell RNA sequencing (scRNA-seq) analyses typically focus on alignment and differential gene expression, being blind to other transcriptome variation. Here we present sc-SPLASH for statistics-first, reference-free discovery on barcoded scRNA-seq and spatial transcriptomics; its independent BKC submodule optimizes barcoded data preprocessing and is approximately 50-fold faster than UMI-tools. sc-SPLASH discovers secreted repeat proteins in immune-like cells of sponge (Spongilla; missing from the reference) and tunicate (Ciona).

UR - https://www.scopus.com/pages/publications/105036671922

U2 - 10.1038/s41587-026-03084-6

DO - 10.1038/s41587-026-03084-6

M3 - Article

C2 - 42020848

AN - SCOPUS:105036671922

SN - 1087-0156

JO - Nature Biotechnology

JF - Nature Biotechnology

ER -

Reference-free discovery with barcoded single-cell sequencing

Abstract

ASJC Scopus subject areas

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