Bruker Expands dia-PASEF® on the timsTOF 4D Proteomics and Epiproteomics Platform to Identify up to 13,000 Protein Groups with 1% FDR
04 April 2022 - 9:10PM
Business Wire
- Innovative TIMScore™ algorithm, combined with TIMS DIA- NN
deep learning, now integrated into ‘Run & Done’ Bruker
PaSER™2022 proteomics system
- Identifies and quantifies more than 8000 protein groups (PG)
in 35 minute-gradient single dia-PASEF runs from ultra-deep
libraries containing over 13,000 PGs in cell-line assays with 1%
FDR (false discovery rate) specificity
- Over 25% more phosphopeptides identified using
TIMScore
At the Proteomic Forum | EuPA 2022, Bruker Corporation
(Nasdaq: BRKR) announced expanded capabilities for deeper proteomic
and epiproteomic coverage, including enhanced phosphopeptide
analysis using the innovative TIMScore algorithm, which is now a
part of the new PaSER 2022 GPU-based platform. The novel TIMScore
algorithm takes advantage of machine learning (ML) to predict CCS
values of tryptic and phosphorylated peptides. Experimentally
measured CCS values are referenced against the predicted CCS value
to call the most probable assignment, thereby increasing peptide
confidence and coverage in high sensitivity applications. The
TIMScore algorithm is especially adept in identifying
phosphopeptides even at the strictest false localization rate (1%
FLR) using LuciPHOr1, where it typically identifies 10%-25% more
phosphopeptides.
The human kinome comprises over 500 kinases and is essential for
catalyzing protein phosphorylation, which during dysregulation is a
known contributor to oncogenesis.2 In a previous human cancer cell
line study by Mann et. al., at least three-fourths of the detected
proteome (7832 out of 10,801 proteins) were found to be
phosphorylated3. In a recent study performed in the Tenzer Lab at
the University Medical Center of the Johannes Gutenberg University
Mainz, some 27,768 phosphopeptides contained 4,672 isobaric
phosphopeptide pairs of which 51% were chromatographically
coeluting. TIMScore could separate 19% of the coeluting isomer
pairs, refining the view of the phosphoproteome of a human
osteosarcoma cell line.
Dr. Stefan Tenzer is Professor of Quantitative Proteomics and
the Head of the Mass Spectrometry Core Facility at the University
Medical Center of the Johannes Gutenberg University Mainz. Dr.
Tenzer commented: “In our lab we use four timsTOF systems to
understand posttranslational modifications and signaling pathways.
TIMScore in PaSER uses machine learning to predict CCS values of
phosphopeptides to decrease peptide ambiguity. The integration of
the TIMScore model in PaSER allows for the seamless search of our
data and provides an impressive increase of over 25% in the number
of identified unique phosphopeptides, enabling deeper
phosphoproteome coverage.”
TIMScore complements the capabilities of TIMS DIA-NN. Both have
been integrated in PaSER 2022 for “Run & Done” dda-PASEF and
dia-PASEF workflows. Using TIMScore and dda-PASEF acquisitions of
K562 and MOLT-4 cell lines, 40 fractions run at short (35 min) and
long (120 min) gradients and filtered to a 1% FDR4 resulted in the
identification of more than 513,000 precursors and 13,114 protein
groups. With access to this experimentally derived and
statistically filtered ultra-deep library, TIMS DIA-NN and short,
35-minute gradient dia-PASEF runs routinely identify >8000
protein groups and >100,000 precursors, setting the stage for
high-throughput translational proteomics.
Dr. Rohan Thakur, President of the Bruker Life-Science Mass
Spectrometry division, added: “It is exciting to see this greater
depth in the biologically relevant phosphoproteome using mass
spectrometry. With ultra-deep protein libraries of over 13k protein
groups (PGs), our customers are now able to quantify over 8000 PGs
with dia-PASEF, using TIMS DIA-NN, short-gradients and small sample
amounts for human cell-line studies in single runs. Since mass
spectrometry is a direct high-specificity readout of actual
peptides and their modifications, and not a surrogate
epitope-binding measurement with unknown FDRs, it has become the
high-specificity method of choice for the study of the
phosphoproteome. With the release of TIMScore and TIMS DIA-NN,
large-scale, high-throughput, label free quantitative
phosphoproteomic studies essential for cell signaling pathway
analysis are now feasible. This will further enhance biomarker
discovery in kinase signaling processes for understanding
pathobiology, including in cancer.”
The PaSER 2022 software includes TIMScore and TIMS DIA-NN for
processing dda-PASEF and dia-PASEF workflows on timsTOF Pro 2,
timsTOF SCP and timsTOF fleX systems. PaSER utilizes data streaming
for dia-PASEF workflows in real-time, supporting ‘run & done’
for high-throughput 4D proteomics and 4D epiproteomics
workflows.
References:
- Fermin D., Walmsley SJ, Gringras AC., Choi, H., Nesvizhskii AI
(2013). LuciPHOr: algorithm for phosphorylation site localization
with false localization rate estimation using modified target-decoy
approach. Mol. Cell Proteomics. Nov 12(11): 3409-19. Doi
10.1074/mcp/. PMID: 23918812.
- Human Kinome study, Savage SR, Zhang B. Using phosphoproteomics
data to understand cellular signaling: a comprehensive guide to
bioinformatics resources. Clin Proteomics. 2020 Jul 11;17:27. doi:
10.1186/s12014-020-09290-x. PMID: 32676006; PMCID: PMC7353784.
- Sharma K, D'Souza RC, Tyanova S, Schaab C, Wiśniewski JR, Cox
J, Mann M. Ultradeep human phosphoproteome reveals a distinct
regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep.
2014 Sep 11;8(5):1583-94. doi: 10.1016/j.celrep.2014.07.036. Epub
2014 Aug 21. PMID: 25159151.
- Elias JE, Gygi SP. Target-decoy search strategy for increased
confidence in large-scale protein identifications by mass
spectrometry. Nat Methods. 2007 Mar;4(3):207-14. doi:
10.1038/nmeth1019. PMID: 17327847.
About Bruker Corporation (Nasdaq: BRKR)
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molecular diagnostics. Please visit www.bruker.com.
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Media Petra Scheffer Bruker Daltonics Marketing
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petra.scheffer@bruker.com
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