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PubMed2026

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Humans↗
PubMed2005

Targeted antitumour therapy--future perspectives.

The advent of targeted therapy presents an unprecedented opportunity for advances in the treatment of cancer. A key challenge will be to translate the undoubted promise of targeted agents into tangible clinical benefits. Achieving this goal is likely to be dependent upon a number of factors. These include continued research to improve our understanding of the heterogeneity and complexity of the tumour microenvironment; refinement of clinical trial design to incorporate nontraditional end points such as the optimum biological dose and health-related quality of life; and the use of technological advancements in proteomics, genomics and biomarker development to better predict tumour types and patient subsets that may be particularly responsive to treatment, as well as enable a more accurate assessment of drug effect at the molecular level. In summary, the future success of targeted agents will require an integrated multidisciplinary approach involving all stakeholders.

Antibodies, Monoclonal↗
PubMed2003

Are coagulation times biomarkers? Data from a phase I study of the oral thrombin inhibitor LB-30057 (CI-1028).

Ecarin clotting time and activated partial thromboplastin time are coagulation tests that meet the definition of a biomarker. Prolongation of these coagulation times closely correlated with blood concentrations of the oral thrombin inhibitor LB-30057 (CI-1028) during a phase 1 study. But this simply reflects their functioning as enzyme inhibition assays of drug concentration. Directly adding the drug to blood results in the same concentration-response relationship. Changes in coagulation tests only demonstrate that ex vivo clot formation has been altered, not that an in vivo process has been affected. To be most informative in drug development, biomarker assays should measure in vivo drug effects, not drug concentrations.

Administration, Oral↗
PubMed2026

Multi-level Transcriptomic and Machine-learning Analyses Identify MZT1 as a Proliferation-associated Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) exhibits substantial molecular heterogeneity and variable clinical outcomes, highlighting the need for biomarkers that reflect core tumor biological processes. Centrosome-associated proteins regulate mitotic fidelity and genome stability, yet their roles in LUAD remain incompletely defined. In this study, we systematically characterized mitotic spindle organizing protein 1 (MOZART1; MZT1) and related family members in LUAD. MATERIALS AND METHODS: We performed integrated analyses combining bulk transcriptomic datasets, survival modeling, gene set enrichment, immune deconvolution, machine-learning based prognostic modeling, and single-cell RNA sequencing. Expression patterns and clinical associations of MZT family genes were evaluated across pan-cancer and LUAD cohorts. RESULTS: MZT family genes were consistently upregulated in tumor tissues, with MZT1 showing the most robust expression pattern. Elevated MZT1 expression was significantly associated with reduced overall survival. Functional analyses revealed coordinated activation of proliferative and genome maintenance pathways, including G2/M checkpoint regulation, E2F and MYC signaling, and DNA repair. A multivariable analysis indicated that the prognostic association of MZT1 was reduced after adjusting for canonical proliferation markers, suggesting partial overlap with established proliferation signals. The LASSO-based Cox model demonstrated stable time-dependent predictive performance at 1-, 3-, and 5-year survival. Immune analyses indicated associations between MZT1 expression and tumor microenvironmental features. Single-cell analysis showed that MZT1 expression was predominantly enriched in malignant epithelial cells and associated with proliferative cellular states. Protein-level validation supported concordance with transcriptomic findings. CONCLUSION: MZT1 is a proliferation-associated marker that integrates clinical risk, transcriptional programs, cellular heterogeneity, and predictive modeling in LUAD, providing a potential framework for biomarker development and risk stratification.

Humans↗
PubMed2000

Recent developments in Barrett's esophagus.

Barrett's esophagus is a precancerous condition in which the squamous esophageal epithelium is replaced by a columnar epithelium. Although different types of columnar epithelium have been described, the most frequently encountered is specialized columnar epithelium or intestinal metaplasia. Most investigators believe that increased cancer risk is only associated with this type. Esophageal adenocarcinoma is increasing in frequency in the United States and in Western Europe. Recent studies highlight the importance of gastroesophageal reflux disease in esophageal adenocarcinoma. Bile-acid reflux may also play a role. Increasing interest has been expressed in short-segment (2-3 cm) Barrett's esophagus. The contribution of short-segment Barrett's esophagus to cancer at the gastroesophageal junction is currently being studied. Although regular surveillance is often recommended, the commonness of Barrett's esophagus makes such a practice impractical for every patient. Biomarker development is needed to identify patients at greatest risk, with p53 a promising candidate based on recent studies. Initial data suggest that redox mechanisms may be involved in Barrett's esophagus. Several methods have recently been described for reversing Barrett's esophagus to squamous epithelium, but the significance of this practice in terms of reducing cancer risk remains to be demonstrated.

Barrett Esophagus↗
PubMed2026

Molecular and immune profiling of HER2-low, HER2 ultra-low, and HER2-null male breast cancer.

BACKGROUND: HER2 expression is described along a biological continuum from null to positive and serves as a critical biomarker for therapeutic guidance in breast cancer (BC). While HER2-low and ultra-low categories have emerged as actionable targets for antibody-drug conjugates (ADCs) in female BC, their molecular and immune characteristics remain largely unexplored in male breast cancer. METHODS: We profiled 214 male breast tumors using next-generation sequencing and whole-transcriptome sequencing to assess mutational, transcriptomic, and immune landscapes. Tumor mutational burden (TMB) was defined as high if > 10 mutations/Mb. Immune cell fractions were inferred using Quantiseq deconvolution. RESULTS: Among 214 samples, 66 (30.8%) were HER2-null, 53 (24.8%) HER2 ultra-low, 80 (37.4%) HER2-low, and 15 (7.0%) HER2-positive. HER2 ultra-low tumors exhibited a higher prevalence of PIK3CA mutations (39.2% vs 22.6%, p ≤ 0.05) compared to HER2-null. No significant differences were observed in TMB-high frequency or PD-L1 expression across subgroups. Immune composition differed primarily between HER2-null and HER2-expressing subgroups: HER2-ultra-low tumors showed higher B-cell infiltration, whereas HER2-null tumors were enriched in neutrophils. Transcriptomic analysis revealed upregulation of selected stemness-associated genes (NANOG, KLF4, POU5F1) and CEACAM1 in HER2-null tumors, while HER2-low and HER2-ultra-low tumors were largely similar across most molecular and immune readouts in this cohort. CONCLUSIONS: HER2-null male breast cancer appears to represent the most biologically divergent subgroup within the HER2-negative spectrum, whereas HER2-low and HER2-ultra-low tumors were largely similar in this cohort. These findings support further investigation of HER2-null disease as a distinct biological state and provide hypothesis-generating data for biomarker development in this rare population.

Male↗
PubMed2026

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans↗
PubMed2026

Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) combined with endocrine therapy have become a therapeutic backbone for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, yet durable disease control is frequently limited by intrinsic and acquired resistance. Canonical tumor-cell mechanisms, including retinoblastoma-pathway escape, cyclin E-cyclin-dependent kinase 2 (CDK2) activation, endocrine adaptation, and phosphoinositide 3-kinase (PI3K)-AKT-mechanistic target of rapamycin (mTOR) signaling, explain only part of this failure because they do not fully capture dynamic immune and stromal remodeling. Preclinical and translational studies indicate that early CDK4/6 inhibition can enhance antigen presentation, activate interferon-related programs, restrain regulatory T cells, and promote a T-cell-inflamed state. These effects are conditional and may not persist during prolonged treatment. Sustained therapy can instead drive heterogeneous resistant niches characterized by stromal remodeling, myeloid recruitment, checkpoint adaptation, and T-cell dysfunction. This immune-state dependence provides a rationale for immune checkpoint blockade, although clinical combinations have shown mixed efficacy and clinically relevant hepatic, pulmonary, and hematologic toxicities. Sequential or lead-in strategies therefore warrant prospective evaluation. Oxidative phosphorylation (OXPHOS) and redox adaptation may sustain selected resistant states and expose context-dependent ferroptotic vulnerabilities. Ferroptosis may connect tumor-cell killing with immune regulation, whereas nanomedicine may improve tumor-selective delivery. Both strategies remain largely preclinical and require further evaluation of pharmacokinetics, biodistribution, toxicity, manufacturability, and immune-cell safety. This Review distinguishes intrinsic from acquired resistance across interpatient, intratumoral, spatial, and temporal dimensions. It integrates tumor-cell escape with cytokine, immune, stromal, vascular, and metabolic remodeling and summarizes emerging therapeutic strategies. We further propose a candidate biomarker-informed framework that integrates genomic profiling, spatial immune architecture, circulating biomarkers, T-cell receptor (TCR) dynamics, transcriptomic and single-cell analyses, artificial intelligence (AI)-assisted multimodal integration, and longitudinal sampling. This framework is intended to support biomarker development and prospective trial design rather than current clinical decision-making, providing a translational basis for testing state-informed and sequence-aware therapeutic strategies.

Humans↗
PubMed2006

Multiplexed protein measurement: technologies and applications of protein and antibody arrays.

The ability to measure the abundance of many proteins precisely and simultaneously in experimental samples is an important, recent advance for static and dynamic, as well as descriptive and predictive, biological research. The value of multiplexed protein measurement is being established in applications such as comprehensive proteomic surveys, studies of protein networks and pathways, validation of genomic discoveries and clinical biomarker development. As standards do not yet exist that bridge all of these applications, the current recommended best practice for validation of results is to approach study design in an iterative process and to integrate data from several measurement technologies. This review describes current and emerging multiplexed protein measurement technologies and their applications, and discusses the remaining challenges in this field.

Animals↗
PubMed2004

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.

PURPOSE: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. EXPERIMENTAL DESIGN: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. RESULTS AND CONCLUSIONS: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.

Antibodies, Monoclonal↗
PubMed2005

Fatty acids from lipids of marine organisms: molecular biodiversity, roles as biomarkers, biologically active compounds, and economical aspects.

Because of their characteristic living environments, marine organisms produce a variety of lipids. Fatty acids constitute the essential part of triglycerides and wax esters, which are the major components of fats and oils. Nevertheless, phospholipids and glycolipids have considerable importance and will be taken into account, especially the latter compounds that excite increasing interest regarding their promising biological activities. Thus, in addition to the major polyunsaturated fatty acids (PUFA) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, a great number of various fatty acids occur in marine organisms, e.g. saturated, mono- and diunsaturated, branched, halogenated, hydroxylated, methoxylated, non-methylene-interrupted. Various unprecedented chemical structures of fatty acids, and lipid-containing fatty acids, have recently been discovered, especially from the most primitive animals such as sponges and gorgonians. This review of marine lipidology deals with recent advances in the field of fatty acids since the end of the 1990s. Different approaches will be followed, mainly developing biomarkers of trophic chains in marine ecosystems and of chemotaxonomic interest, reporting new structures, especially those with biological activities or biosynthetic interest. An important part of this review will be devoted to the major PUFA, their relevance to health and nutrition, their biosynthesis, their sources (usual and promising) and market.

Bacteria↗
PubMed2006

Sonic Hedgehog signaling in advanced prostate cancer.

The Hedgehog family of growth factors activate a highly conserved signaling system for cell-cell communication that regulates cell proliferation and differentiation during development. Abnormal activation of the Hedgehog pathway has been demonstrated in a variety of human tumors, including those of the skin, brain, lung and digestive tract. Hedgehog pathway activity in these tumors is required for cancer cell proliferation and tumor growth. Recent studies have uncovered the role for Hedgehog signaling in advanced prostate cancer and demonstrated that autocrine signaling by tumor cells is required for proliferation, viability, and invasive behavior. The level of Hedgehog activity correlates with the severity of the tumor and is both necessary and sufficient for metastatic behavior. Blockade of Hedgehog signaling leads to tumor shrinkage and remission in preclinical tumor xenograft models. Thus, Hedgehog signaling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring.

Animals↗
PubMed2006

Assessment of branched-chain amino Acid status and potential for biomarkers.

BCAAs are not synthesized in the body in humans, but they are crucial in protein and neurotransmitter synthesis. The protein anabolic role of BCAAs seems to be mediated not only by their important role as a promoter of the translation process (and possibly acting at the transcription level) but also by inhibition of protein degradation. Leucine may play a critical role in these signaling pathways. Supplementation with BCAAs spares lean body mass during weight loss, promotes wound healing, may decrease muscle wasting with aging, and may have beneficial effects in renal and liver disease. BCAA supplementation is extensively used in the athletic field with the assumption of improved performance and muscle mass. Measuring serum BCAAs has limited clinical utility beyond the controlled setting because levels are affected by a variety of clinical states, and optimal levels in these scenarios have not been completely elucidated. We discuss the effects diet, hormones, stress, aging, and renal or liver dysfunction have on BCAA levels and how understanding the biological effects of BCAAs may help to develop biomarkers of BCAA status. We also discuss potential biomarkers of BCAA status.

Aging↗
PubMed2006

TMABoost: an integrated system for comprehensive management of tissue microarray data.

In the last decade, high-throughput technologies such as DNA and tissue microarrays (TMAs) have become a means of large-scale investigation of gene expression, providing a plethora of new biomedical data in a relatively short time. Data collection and organization are critical aspects in this process to ensure the quality and reliability of future data interpretation. In this work, we propose a comprehensive approach to handle TMA data with the aim of supporting and promoting biomarker development. We describe a web-based system for the complete management of tissue microarray data in the field of pathology. The system has been in use since June, 2003. Our approach includes automatic localization and identification of tissue microarray samples, and quantitative image analysis that allows high-throughput screening of TMAs by ensuring nonsubjective measures and novel prognosis associations. In this paper, we present the architecture and the components of this system.

Algorithms↗
PubMed2006

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery.

The SELDI-TOF technique was used to profile serum proteins from Type 1 diabetes (T1D) patients and healthy autoantibody-negative (AbN) controls. Univariate and multivariate analyses were performed to identify putative biomarkers for T1D and to assess the reproducibility of the SELDI technique. We found 146 protein/peptide peaks (581 total peaks discovered) in human serum showing statistical differences in expression levels between T1D patients and controls, with 84% of these peaks showing technical replication. Because individual proteins did not offer great power for disease prediction, we used our model averaging approach that combines the information from multiple multivariate models to accurately classify T1D and control subjects (88.9% specificity and 90.0% sensitivity). Analyses of a test subset of the data showed less accuracy (82.8% specificity and 76.2% sensitivity), although the results are still positive. Unfortunately, no multivariate model could be replicated using the same samples. This first attempt of high throughput analyses of the human serum proteome in T1D patients suggests that model averaging is a viable method for developing biomarkers; however, the reproducibility of SELDI-TOF is currently not sufficient to be used for classification of complex diseases like T1D.

Adolescent↗
PubMed2025

T cell subsets of urine-derived lymphocytes (UDLs) serve as an indicator of TILs and reflect immunological sex differences in bladder cancer.

BACKGROUND: Bladder cancer is unique among visceral malignancies in that urine, which can be easily obtained, has prolonged contact with bladder tumors. Urinary biomarkers offer the potential to provide insight into the host and tumor immune microenvironment to guide therapeutic strategies. We evaluated the immune cellular composition of urine (urine-derived lymphocytes (UDLs)) versus tumor (tumor-infiltrating lymphocytes (TILs)). METHODS: We employed high-dimensional flow cytometry analyses on immune cells from tumors (TILs), urine (UDLs), and peripheral blood (peripheral blood mononuclear cells) among patients with bladder cancer. We performed multiplexed immunofluorescence (mIF) of matched tumors to provide spatial context to our findings, comparing deep/invasive and superficial/urine-facing regions of matched tumors. RESULTS: Our findings suggest that the CD4+ and CD8+ T cell subsets of UDLs characterized by flow cytometry had similar phenotypic profiles to those found in TILs (cell clusters quantified by multidimensional scaling and differentiation states). Results of mIF imaging with a panel of phenotypic and functional T cell markers suggested that UDLs reflected TILs in both superficial and deep tumor sections. We also found sex-dependent patterns in TILs and UDLs, indicating the male bladder cancer tumor microenvironment is enriched in exhausted CD4+ and CD8+ T cells, while the female bladder cancer microenvironment is enriched for activated T cells. CONCLUSIONS: Assessment of UDLs opens avenues of non-invasive biomarker development in clinical settings where bladder cancer TILs are hypothesized to predict clinical response. UDLs may also reflect sex-based differences in antitumor immunity.

Humans↗
PubMed2000

Laryngeal mucosa of head and neck cancer patients shows increased DNA damage as detected by single cell microgel electrophoresis.

Major risk factors for cancer of the oral cavity, pharynx and larynx are smoking and excess alcohol consumption. Since long-term survival rates of head and neck cancer patients have not substantially been improved, new preventive strategies including the use of cancer chemopreventive agents have to be developed. With the aim of developing biomarkers which can verify the efficacy of chemopreventive interventions, a standardised alkaline microgel electrophoresis (MGE) assay was applied as a sensitive and rapid tool to detect DNA damage on a single cell level. Macroscopically normal laryngeal mucosa biopsies obtained by surgery from head and neck cancer patients (n=29) and from hospital controls (n=22) were analysed by MGE in a pilot study. As compared to controls, cells from head and neck cancer patients showed a significantly elevated DNA damage without any further genotoxic treatment (P<0.01). We conclude that this increased background DNA damage in laryngeal epithelia could result from genetic alterations caused by smoking and alcohol leading, in accord with the field cancerisation hypothesis, to a gradual decrease of genomic stability and malignancy. MGE should now be explored as a rapid screening method in larger clinical studies: (i) to identify high-risk subjects carrying cells with decreased genomic stability and (ii) to verify the efficacy of chemopreventive regimens to prevent or slow down the development of head and neck cancer in high-risk persons.

Adult↗
PubMed2025

Methylome profiling of cell-free DNA during the early life course in (un)complicated pregnancies using MeD-seq: Protocol for a cohort study embedded in the prospective Rotterdam periconception cohort.

INTRODUCTION: Placental DNA methylation differences have been associated with timing in gestation and pregnancy complications. Maternal cell-free DNA (cfDNA) partly originates from the placenta and could enable the minimally invasive study of placental DNA methylation dynamics. We will for the first time longitudinally investigate cfDNA methylation during pregnancy by using Methylated DNA Sequencing (MeD-seq), which is compatible with low cfDNA levels and has an extensive genome-wide coverage. We aim to investigate DNA methylation in placental tissues and cfDNA during different trimesters in uncomplicated pregnancies, and in pregnancies with placental-related complications, including preeclampsia and fetal growth restriction. Identified gestational-age and disease-specific differentially methylated regions (DMRs) could lead to numerous applications including biomarker development. METHODS AND ANALYSIS: Our study design involves three sub-studies. Sub-study 1 is a single-centre prospective, observational subcohort embedded within the Rotterdam Periconception cohort (Predict study). We will longitudinally collect maternal plasma in each trimester and during delivery, and sample postpartum placentas (n = 300). In sub-study 2, we will prospectively collect first and second trimester placental tissues (n = 10 per trimester). In sub-study 3 we will retrospectively collect plasma after non-invasive prenatal testing (NIPT) in an independent validation case-control cohort (n = 30-60). A methylation-dependent restriction enzyme (LpnPI) will be used to generate DNA fragments followed by sequencing on the Illumina NextSeq2000 platform. DMRs will be identified in placental tissues and cell types, and in cfDNA related to gestational-age or placental-related complications. (Paired) placental methylation profiles will be correlated to DMRs in cfDNA to aid tissue-of-origin analysis. We will establish a methylation score to predict associated diseases. DISCUSSION: This study will provide insights in placental DNA methylation dynamics in health and disease, and could lead to clinical relevant biomarkers.

Humans↗