Optimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference

Hui Peng, He Wang, Weijia Kong, Jinyan Li () and Wilson Wen Bin Goh ()
Additional contact information
Hui Peng: Nanyang Technological University
He Wang: Nanyang Technological University
Weijia Kong: Nanyang Technological University
Jinyan Li: Chinese Academy of Sciences
Wilson Wen Bin Goh: Nanyang Technological University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Identification of differentially expressed proteins in a proteomics workflow typically encompasses five key steps: raw data quantification, expression matrix construction, matrix normalization, missing value imputation (MVI), and differential expression analysis. The plethora of options in each step makes it challenging to identify optimal workflows that maximize the identification of differentially expressed proteins. To identify optimal workflows and their common properties, we conduct an extensive study involving 34,576 combinatoric experiments on 24 gold standard spike-in datasets. Applying frequent pattern mining techniques to top-ranked workflows, we uncover high-performing rules that demonstrate optimality has conserved properties. Via machine learning, we confirm optimal workflows are indeed predictable, with average cross-validation F1 scores and Matthew’s correlation coefficients surpassing 0.84. We introduce an ensemble inference to integrate results from individual top-performing workflows for expanding differential proteome coverage and resolve inconsistencies. Ensemble inference provides gains in pAUC (up to 4.61%) and G-mean (up to 11.14%) and facilitates effective aggregation of information across varied quantification approaches such as topN, directLFQ, MaxLFQ intensities, and spectral counts. However, further development and evaluation are needed to establish acceptable frameworks for conducting ensemble inference on multiple proteomics workflows.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47899-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47899-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47899-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().