Cited by 37Advanced Proteomics Techniques and ApplicationsBioinformatics and Genomic NetworksAdvanced Biosensing Techniques and Applications

Integrated Identification and Quantification Error Probabilities for Shotgun Proteomics

Open access
The, Matthew, Käll, Lukas·2019·Molecular & Cellular Proteomics

Published version of a preprint

Abstract

Abstract Protein quantification by label-free shotgun proteomics experiments is plagued by a multitude of error sources. Typical pipelines for identifying differentially expressed proteins use intermediate filters in an attempt to control the error rate. However, they often ignore certain error sources and, moreover, regard filtered lists as completely correct in subsequent steps. These two indiscretions can easily lead to a loss of control of the false discovery rate (FDR). We propose a probabilistic graphical model, Triqler , that propagates error information through all steps, employing distributions in favor of point estimates, most notably for missing value imputation. The model outputs posterior probabilities for fold changes between treatment groups, highlighting uncertainty rather than hiding it. We analyzed 3 engineered datasets and achieved FDR control and high sensitivity, even for truly absent proteins. In a bladder cancer clinical dataset we discovered 35 proteins at 5% FDR, whereas the original study discovered 1 and MaxQuant/Perseus 4 proteins at this threshold. Compellingly, these 35 proteins showed enrichment for functional annotation terms, whereas the top ranked proteins reported by MaxQuant/Perseus showed no enrichment. The model executes in minutes and is freely available at https://pypi.org/project/triqler/ .

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/mcp.ra118.001018

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Outlier-exclusion methods improve protein concentration estimates but still report only one protein quantity and ignore peptides that do not agree with that value.

    “While these all demonstrate improved protein concentration estimates, they still only report a single protein quantity and ignore peptides that do not agree with that single value.”
  • Several proposed methods exclude peptide measurements from the aggregate protein quantity when they are outliers relative to other peptides mapping to the same protein-coding gene.

    “The approach of several proposed methods focuses on the exclusion of peptide measurements from inclusion in the aggregate protein quantity if they are outliers from other peptide measurements mapping to the same protein coding gene.(28–33)”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
The, M., & Käll, L.
Affiliations
Science for Life Laboratory (SE)
Corresponding author
Käll, Lukas
Venue
Molecular & Cellular Proteomics
Publisher
Elsevier BV
Published
2019-03
Volume
18
Issue
3
Pages
561-570
ISSN
1535-9476 (ISSN-L)
OpenAlex
W2949908578
Cited by
37
References
42
Citations by year
2026: 5 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 2 · 2019: 3
FWCI
1.40
Type
journal article
Language
en
Open access
Locations
  • Molecular & Cellular Proteomics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Vetenskapsrådet (2017–04030)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
Keywords
label-free quantitative proteomics, false discovery rate control, error propagation, probabilistic graphical models, missing data imputation, bladder cancer
MeSH terms
Algorithms, Bayes Theorem, Urinary Bladder Neoplasms, Humans, Models, Theoretical, Databases, Protein, Proteomics, Tandem Mass Spectrometry

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review