Last Updated
23 September 2021

Proteograph Product Suite used for unbiased and deep plasma proteome profiles

1 © Seer 2021
~20K
Genes
~200K
Transcripts
~1M
Proteoforms
STATIC
DYNAMIC
Genome Proteome
Transcription
RNA processing
Translation
Post-translational
modification (PTM)
Protein-protein
interactions (PPI)
Transcriptome Interactome
~695M
Genetic variants
catalogued
Comprehensive coverage of the proteome remains elusive, because of proteoforms
arising from alternative splicing, allelic variation, and protein modifications.
Tryptic peptides
Plasma Proteins Nanoparticles Protein coronas
Data analysis Microflow SWATH
LC/MS analysis
MaxQuant 5ug
Digestion
NSCLC Control
n=80
n=61
Seer Core technology and Proteograph Product Suite
provides unbiased, deep, and rapid proteomics at scale
Challenge Solution
Proteograph
Assay
Deep, Rapid and Unbiased Plasma Proteomics with the Proteograph™
Product Suite Enables Proteogenomic Studies with Differential Analysis
of Proteoforms
Margaret K. R. Donovan, John E. Blume, Marwin Ko, Ryan W. Benz, Theodore L. Platt, Juan C. Cuevas, Serafim
Batzoglou, Asim Siddiqui and Omid C. Farokhzad
Margaret Donovan, Ph.D.
Bioinformatics Scientist, Seer
Mdonovan@seer.bio
2 © Seer 2021
Utilizing Proteograph Platform to interrogate protein isoforms in a non-small
cell lung cancer (NSCLC) plasma proteome study
1Blume et al. Nat. Comm. (2020)
Median 8 peptides for each of the 1,992 proteins observed in at least 25% of the 141 subjects of NSCLC study1
Early NSCLC
Control (Healthy)
Number of Subjects
n=80
n=61
Percentage of Samples
in Which Protein Group Detected
1992 Protein Group Counts
2499
Number of Peptides Detected per Protein
Number of Proteins
Median 8
Study subjects Detected protein groups Detected peptides
3 © Seer 2021
Identification of putative protein isoforms using peptide abundance
2Deutsch et al. J. Proteome Res.(2018)
16 putative protein isoforms show known and novel associations with lung carcinoma targets and span the dynamic range
Protein X
Relative
Abundance
Peptide
0.0
1.0
0.5
***
Detected Peptides Peptide Peptide Peptide Peptide Peptide Peptide
*** ***
16 candidate protein isoforms
Protein isoform identification strategy
Associated Open Target Score
16 Candidate Proteins Ranked by the HPPP2
15/3486
Matched
Estimated ng/mL
C1R
C4A
ITIH1
THBS3
HADHA
FERMT3
RTN4
LDHB
PRG4
COL6A3
BMP1
FLNA
TLN1
VCL
RAP1B
APOB
0.0 0.2 0.4 0.6 0.8
Associated Open Targets Score
16 candidate proteins
Open targets score for lung carcinoma targets
Intensity rank
4 © Seer 2021
Proteogenomic Studies at Scale with an unbiased, deep
and rapid method
31000 Genomes (2015)
Peptide variant identification using personalized libraries
Detection of peptide variants in
NSCLC-associated proteins
APOB COL6A3 FERMT3 FLNA ITIH1 PRG4 TLN1
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
N variant peptides
Putative protein isoforms with detected variant peptides
Study Design
Co-morbid
n=4 n=11 n=5 n=9
Healthy
NSCLC(early)
NSCLC(late)
WES
(personalized library)
Proteome
Peptide Variant Identification
N Variants
(log10)
0
25000000
50000000
75000000
100000000
0.00 0.25Alternate 0A.5l0lele Freque0n.7c5y 1.00
AF across 464 protein variants from 29 subjects vs. 1KG3
Protein variants across 29 subjects
464 protein variants from 29 subjects
29 subjects
1KG
CO−MORBID HEALTHY NSCLC_EARLY NSCLC_LATE
008−0009
008−0014
002−0081
009−0043
009−0006
001−0044
009−0042
020−0091
014−0066
014−0036
009−0045
020−0099
014−0049
020−0079
020−0100
029−0005
005−0032
007−0025
021−0004
005−0019
018−0004
022−0016
013−0025
010−0043
009−0041
013−0023
005−0040
010−0042
010−0049
0
50
100
150
N variant peptides
Protein variants across 29 subjects
5 © Seer 2021
Conclusions
Proteograph Product Suite for Proteogenomic Analyses
Proteograph can generate unbiased and deep plasma proteome profiles that
enable identification of protein variants and peptides present in plasma
at a scale sufficient to enable population-scale proteomic studies.
Using the Proteograph Product Suite,
we detected 2499 protein groups,
with 1,992 in 25% of the subjects, and
21,959 peptides in total with median 8
peptides per protein across all 141
subjects (control vs. early NSCLC
plasma samples)
We identified 16 candidate protein
isoforms associated with lung cancer
(both known and novel targets) that
span across the dynamic range,
including one not reported in the
Human Plasma Proteome Project
Proteogenomic analysis of a subset of
the NSCLC subjects identified 464
peptide variants, of which map to 7 out
of the 16 lung cancer-associated
candidate protein isoforms