ADTnorm: Robust Integration of Single-cell Protein Measurement across CITE-seq Datasets
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Serval ID
serval:BIB_8A286CBE32FB
Type
Autre: use this type when nothing else fits.
Collection
Publications
Institution
Title
ADTnorm: Robust Integration of Single-cell Protein Measurement across CITE-seq Datasets
ISSN
2693-5015 (Electronic)
ISSN-L
2693-5015
Issued date
08/07/2024
Language
english
Abstract
CITE-seq enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm (https://github.com/yezhengSTAT/ADTnorm), a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations with negative- and positive-expression of surface protein markers across 13 public datasets, effectively removing technical variation across batches and improving cell-type separation. ADTnorm enables efficient integration of public CITE-seq datasets, each with unique experimental designs, paving the way for atlas-level analyses. Beyond normalization, ADTnorm includes built-in utilities to aid in automated threshold-gating as well as assessment of antibody staining quality for titration optimization and antibody panel selection. Applying ADTnorm to a published COVID-19 CITE-seq dataset allowed for identifying previously undetected disease-associated markers, illustrating a broad utility in biological applications.
Pubmed
Create date
07/08/2024 7:57
Last modification date
08/08/2024 6:28