Nature Genetics Study Validates Seer’s Proteograph Platform as Essential for Turning Genetic Signals Into Reliable Drug Targets and Biomarkers

Rhea-AI Summary

Seer (NASDAQ: SEER) announced a Nature Genetics study (Nov 2025) validating its Proteograph product suite for population-scale, peptide-level mass spectrometry proteomics. The GWAS profiled ~1,600 blood samples (discovery n=1,260; replication n=325), detecting 5,753 proteins and quantifying 1,980 in ≥80% of participants. Researchers identified 364 pQTLs, 102 replicated, and 35 novel signals. The study found up to one-third of affinity-based pQTLs from single platforms failed mass spectrometry replication, showing peptide-level measurement reduces epitope-related artifacts and improves confidence for drug-target and biomarker discovery.

Implication: peptide-level MS can distinguish true protein regulation from assay artifacts, strengthening translational proteogenomics.

Positive

• Cohort size of ~1,600 samples supports population-scale analysis
• 5,753 proteins detected by Proteograph
• 1,980 proteins quantified in ≥80% of participants
• 364 pQTLs identified across the dataset
• 102 pQTLs replicated in independent cohort
• 35 previously unreported replicated pQTLs

Negative

• Up to one-third of single-platform affinity pQTLs did not replicate by MS

Insights

Proteomics–Genetics Integrator

Mass-spectrometry peptide-level GWAS validates Proteograph as a higher-fidelity assay for mapping gene→protein links.

The study measured ~1,600 blood samples and detected 5,753 proteins, quantifying 1,980 in at least 80% of participants, then identified 364 pQTLs with 102 replicating in an independent cohort; these concrete figures show the platform achieved population-scale coverage and internal replication. By measuring peptides directly, the method avoids epitope effects that can confound affinity reagents, so the business mechanism is clear: peptide-level mass spectrometry distinguishes true abundance changes from binding artifacts, improving the fidelity of protein–genetic maps.

Dependencies and risks include cohort size and replication rates: only 102 of 364 pQTLs replicated, so many associations remain cohort-dependent; the analysis used a discovery cohort of 1,260 and replication of 325, which constrains power for rarer signals. Key items to watch include broader replication in larger, ancestrally diverse cohorts and confirmation that peptide-level calls consistently annotate affinity-platform results; expect follow-up validation work over the next 12–36 months and note the publication date November 2025.

Translational Drug-Discovery Analyst

Peer-reviewed MS validation reduces risk of following false drug targets reported by affinity assays.

For drug and biomarker discovery, peptide-level confirmation cuts technical noise by filtering epitope-induced false positives; the study reports up to one-third of single-affinity-platform pQTLs failing MS replication, which directly affects target prioritization and de‑risking workflows. This makes the Proteograph platform a validation layer that can reduce wasted preclinical effort by focusing resources on genetically supported protein changes that reflect real biology.

Risks and next steps include scaling validation across larger clinical cohorts and demonstrating that MS-confirmed targets translate into functional biology and therapeutic modulation. Track replication counts, the proportion of affinity-reported pQTLs confirmed by mass spectrometry, and subsequent use of MS-validated signals in Mendelian randomization or target-to-clinic programs over the coming 1–3 years; those milestones will determine practical impact for drug pipelines.

Large-scale GWAS across ~1,600 samples shows how peptide-level mass spectrometry distinguishes true protein changes from potential binding artifacts resulting from affinity-based approaches, establishing accuracy as the foundation for downstream discovery

REDWOOD CITY, Calif., Dec. 01, 2025 (GLOBE NEWSWIRE) -- Seer, Inc. (Nasdaq: SEER), the pioneer and trusted partner for deep, unbiased proteomic insights, today announced the publication in Nature Genetics of a large genome-wide association study (GWAS) that used the company’s Proteograph^® Product Suite to measure proteins at peptide-level resolution and map their genetic determinants. The study, led by Karsten Suhre, PhD, of Weill Cornell Medicine–Qatar, with collaborators from Harvard Medical School/Brigham and Women’s Hospital, Seer, and TruDiagnostic, provides the strongest evidence to date that mass spectrometry validation is essential for turning genomic signals into reliable drug targets and clinical biomarkers. Without mass spectrometry validation, as many as one-third of protein–gene associations reported by affinity-based assays do not replicate, highlighting the necessity of accuracy in proteogenomics.

The analysis included ~1,600 blood samples representing multiple ethnic backgrounds. A discovery cohort of 1,260 and an independent replication cohort of 325 were profiled using Seer’s Proteograph workflow. Across these samples, 5,753 proteins were detected, and 1,980 were quantified in at least 80 percent of participants.

From these data, the researchers identified 364 protein quantitative trait loci (pQTLs) genetic variants associated with protein abundance. Of these, 102 replicated in the independent cohort. 35 of the replicated signals were previously unreported, extending the catalog of genetic regulation of proteins.

Affinity reagents have been used in proteomics to measure a predetermined panel of proteins in large cohorts and have generated thousands of reported pQTLs. But when protein-altering genetic variants change the binding site of affinity reagents, these methods can register erroneous signals as the binding strength of the affinity reagent to the protein is diminished. These so-called epitope effects can produce apparent associations between protein expression and genetic variants that do not represent true biology.

By measuring proteins directly at the peptide level, the Proteograph’s mass spectrometry approach made it possible to test whether a genetic variant truly altered protein expression, mitigating the confounding epitope effect.

“The Proteograph platform made it possible to perform population-scale mass spectrometry proteomics with the depth and reproducibility needed for genetic association studies,” said Dr. Suhre. “By measuring proteins directly at the peptide level, we could distinguish true biological effects from assay artifacts—yielding a more reliable map from genes to proteins to disease pathways.”

To contextualize the findings, the study compared mass spectrometry results with two of the largest affinity-based proteomics resources. The comparison revealed a clear pattern:

• pQTLs consistently reported across multiple affinity platforms were confirmed by mass spectrometry.
  
• Up to one-third of associations reported by a single affinity platform did not replicate when tested by mass spectrometry.
  
  

“This study demonstrates that mass spectrometry-based analysis is crucial for proteomics,” said Serafim Batzoglou, PhD, Chief Data Officer at Seer. “By providing peptide-level confirmation at scale, the Proteograph establishes protein measurements that lead to novel genetic associations and help annotate the accuracy of affinity-based pQTL predictions.”

For academic researchers conducting GWAS and Mendelian randomization studies, the message is direct: datasets built only on affinity reagents may contain a substantial fraction of associations that do not represent true protein abundance. Without validation, downstream analyses risk drawing causal inferences from epitope-induced artifacts.

For drug discovery and biomarker development, peptide-level validation strengthens confidence that selected targets represent genuine biology, not technical noise. Reliable associations reduce wasted effort and increase the likelihood that preclinical findings will hold in clinical settings.

For translational research, the study demonstrates how mass spectrometry and affinity reagents can be used together, with mass spectrometry stratifying the level of reliability of affinity-based predictions.

For patients, this rigor means a higher probability that tomorrow’s therapies are built on real biology. Together, they create a path toward comprehensive and trustworthy protein–genetic maps.

This publication marks the validation stage. The Nature Genetics study provides peer-reviewed evidence that mass spectrometry can systematically resolve artifacts and confirm which associations are robust.

The transformation comes in what this enables. As proteomics expands to larger populations and integrates with genomics, epidemiology, and clinical records, the utility of those datasets depends on accuracy. By anchoring discovery on peptide-level confirmation, Seer positions proteomics to become a population-ready science that supports drug targets, biomarkers, and translational medicine with the rigor required for clinical impact.

Article information

Title: A genome-wide association study of mass spectrometry proteomics using the Seer Proteograph platform
Journal: Nature Genetics, November 2025 (online)
Authors: Suhre K., Lasky-Su J., et al., including Seer scientists

About Seer

Seer, Inc. (Nasdaq: SEER) sets the standard in deep, unbiased proteomics—delivering insights with scale, speed, precision, and reproducibility previously unattainable by other proteomic methods. Seer’s Proteograph Product Suite uniquely integrates proprietary engineered nanoparticles, streamlined automation instrumentation, optimized consumables, and advanced analytical software to solve challenges conventional methods have failed to overcome. Traditional proteomic technologies have struggled with inconsistent data, limited throughput, and prohibitive complexity, but Seer’s robust and scalable workflow consistently reveals biological insights that others do not. Seer’s products are for research use only and are not intended for diagnostic procedures. For more information about Seer’s differentiated approach and ongoing leadership in proteomics, visit www.seer.bio.

Media Contact:
Patrick Schmidt
pr@seer.bio

Investor Contact:
Carrie Mendivil
investor@seer.bio

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/ae65f47f-3263-4c92-ae93-f0f8d4ea62e4

FAQ

What did Seer (SEER) report in the Nature Genetics GWAS published Nov 2025?

The study used Proteograph to profile ~1,600 samples, detected 5,753 proteins, and identified 364 pQTLs with 102 replicated.

How many proteins did Proteograph quantify in the SEER GWAS?

Proteograph quantified 1,980 proteins in at least 80% of participants.

What replication results did the SEER Nature Genetics study report for pQTLs?

Of 364 pQTLs discovered, 102 replicated in an independent cohort and 35 were novel.

What does the SEER study say about affinity-based pQTL findings?

The study found up to one-third of associations from a single affinity platform failed to replicate by mass spectrometry.

How does peptide-level mass spectrometry affect drug-target selection for SEER (SEER)?

Peptide-level MS reduces epitope artifacts, increasing confidence that selected targets reflect true biology, not assay noise.

Which sample sizes were used in Seer's Proteograph GWAS (SEER)?

A discovery cohort of 1,260 samples and an independent replication cohort of 325 samples.