Cancer detection is challenging, especially in patients with diffuse symptoms that overlap with non-malignant conditions. Here we show that plasma protein profiling can identify cancer among patients with non-specific symptoms. Using proximity extension assay-based proteomics of 1463 plasma proteins from 456 patients presenting with non-specific symptoms sampled prior to cancer diagnostic work-up and diagnosis, we identify 29 proteins associated with new cancer diagnoses. We develop a model able to stratify 160 cancer cases and 296 non-cancer cases with an area under the curve of 0.80, maintaining performance (0.82) in an independent replication cohort of 238 patients. The model also distinguishes cancer from autoimmune, inflammatory and infectious diseases. Designed as a triage tool, our model based on a blood test could help prioritize patients at higher cancer risk for rapid and highly sensitive diagnostic modalities such as positron emission tomography-computed tomography. These findings emphasize the potential of blood proteome profiling to support timely diagnosis and transform clinical medicine.

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. In this study, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and body mass index, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8262 individuals and up to 5416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.

The human blood proteome offers a powerful window into health and disease, allowing for precision medicine efforts, involving early detection of disease, stratification of patients, and monitoring of therapeutic regimes. Here, we report on the analysis of 28 diseases and 2,254individuals using two next generation blood profiling platforms, Proximity Extension Assay and SomaScan, with analysis of over 5,400 and 9,500 protein targets, respectively. The study enables cross-platform comparison of disease-associated profiles and predictive models to find patients with a particular disease. We also cover the longitudinal analysis of children through puberty and the dramatic changes in women during pregnancy. The study includes the analysis of a longevity cohort with healthy old-aged individuals, and we report on a revised model for biological age based on a selected subset of the circulating proteome. The data is visualized in a new version of the open access Blood Resource as part of the Human Protein Atlas allowing comparisons of the two analytical platforms to explore the proteome profiles across the blood from healthy individuals and patients with diseases.

Motivation: Exploration of large-scale biological datasets remains a central challenge in computational biology. While many tools are available, they are often developed in isolation, leading to fragmented workflows, duplicated efforts, and limited reproducibility. There is a pressing need for flexible, standardized solutions that unify exploratory data analysis and biomarker discovery across diverse platforms.

Results: We present HDAnalyzeR, a user-friendly and extensible R package for the streamlined analysis of high-dimensional biological data. HDAnalyzeR provides modular, reproducible workflows that support a range of analyses, from quality control and dimensionality reduction to differential expression and enrichment analysis. The package features built-in visualization, metadata-aware modeling, and seamless integration with interactive apps and learning resources. We also present two case studies, where HDAnalyzeR dramatically reduced analysis time and code complexity while providing biologically meaningful insights, such as classification of blood cancer types with AUC = 1.0 and identification of thousands of solid tumor-associated genes. HDAnalyzeR is designed to support both beginner users and experienced bioinformaticians, promoting transparency, reproducibility, and publication-quality output.

Availability and implementation: HDAnalyzeR is freely available both as an open-source R package at https://github.com/kantonopoulos/HDAnalyzeR and a web application at https://hdanalyzer.serve.scilifelab.se.