Estimating protein isoform abundances with PAQu

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-22
DOI
https://doi.org/10.64898/2026.04.20.719668
Primary Topic
Advanced Proteomics Techniques and Applications
Type
article
Field-Weighted Citation Impact
0.00
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article

Estimating protein isoform abundances with PAQu

Matthew L. MacDonald, Lambertus Klei, Lorenzo Testa, Kathryn Roeder et al.
bioRxiv (Cold Spring Harbor Laboratory)
Advanced Proteomics Techniques and Applications
article

Estimating protein isoform abundances with PAQu

Matthew L. MacDonald, Lambertus Klei, Lorenzo Testa, Kathryn Roeder, David A. Lewis, Anastasia Yocum, Alesia Rengle, Bernie Devlin
article en

Abstract

A single gene can encode multiple versions of a protein, dubbed isoforms, with varying functionality. Cellular control of isoform abundances is critical for multiple aspects of biology and is only partially regulated by transcript levels. While long-read sequencing facilitates transcript quantification, quantifying the resulting protein isoforms on a large scale is a major challenge, complicating biological interpretation of transcript alterations. Standard "bottom up" mass spectrometry can assess only short portions of isoforms called peptides, and these peptides often map onto more than one isoform. We introduce PAQu , a novel Bayesian method that leverages multiomic information from the peptidome and transcriptome to provide accurate estimates of isoform abundance even when peptide mapping is ambiguous. PAQu offers several advantages over existing methods in a unified framework. It provides uncertainty quantification, integrates multiomic information for improved accuracy, and provides a rigorous framework for hypothesis testing. Extensive simulations show that PAQu consistently outperforms competing methods in detecting differentially expressed protein isoforms and estimating their abundances. We use PAQu to investigate differences in isoform abundance levels between people with schizophrenia and control subjects, confirming a long held hypothesis that levels of the C4A isoform of Complement Component 4 are increased in schizophrenia while C4B is not. These results demonstrate that PAQu can identify significant variations in isoform abundance levels not previously possible.

bioRxiv (Cold Spring Harbor Laboratory)
Scuola Superiore Sant'Anna (IT), University of Pittsburgh (US), Wagner College (US), Carnegie Mellon University (US)
Openalex Percentile: Top 15%
Advanced Proteomics Techniques and Applications
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