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Cell Systems Aug 2021There is an avalanche of biomedical data generation and a parallel expansion in computational capabilities to analyze and make sense of these data. Starting with genome... (Review)
Review
There is an avalanche of biomedical data generation and a parallel expansion in computational capabilities to analyze and make sense of these data. Starting with genome sequencing and widely employed deep sequencing technologies, these trends have now taken hold in all omics disciplines and increasingly call for multi-omics integration as well as data interpretation by artificial intelligence technologies. Here, we focus on mass spectrometry (MS)-based proteomics and describe how machine learning and, in particular, deep learning now predicts experimental peptide measurements from amino acid sequences alone. This will dramatically improve the quality and reliability of analytical workflows because experimental results should agree with predictions in a multi-dimensional data landscape. Machine learning has also become central to biomarker discovery from proteomics data, which now starts to outperform existing best-in-class assays. Finally, we discuss model transparency and explainability and data privacy that are required to deploy MS-based biomarkers in clinical settings.
Topics: Artificial Intelligence; Biomarkers; Mass Spectrometry; Proteomics; Reproducibility of Results
PubMed: 34411543
DOI: 10.1016/j.cels.2021.06.006 -
Journal of Clinical Oncology : Official... Aug 2022There exists a tremendous opportunity in identifying and determining the appropriate predictive and prognostic biomarker(s) for risk stratification of patients with... (Review)
Review
There exists a tremendous opportunity in identifying and determining the appropriate predictive and prognostic biomarker(s) for risk stratification of patients with colorectal cancers (CRCs). Circulating tumor DNA (ctDNA) has emerged as a promising prognostic and possibly predictive biomarker in the personalized management of patients with CRCs. The disease is particularly suited to a liquid biopsy-based approach since there is a great deal of shedding of circulating tumor fragments (cells, DNA, methylation markers, etc). ctDNA has been shown to have several potential applications, including detecting minimal residual disease (MRD), monitoring for early recurrence, molecular profiling, and therapeutic response prediction. The utility of ctDNA has broadened from its initial use in the advanced/metastatic setting for molecular profiling and detection of acquired resistance mechanisms, toward identifying MRD, as well as early detection. Prospective studies such as CIRCULATE, COBRA, Dynamic II/III, and ACT3 are underway in the MRD setting to further understand how ctDNA may be used to inform clinical decision making using both tumor-informed and tumor-agnostic platforms. These prospective studies use ctDNA to guide management of patients with CRC and will be critical to help guide how and where ctDNA should or should not be used in clinical decision making. It is also important to understand that there are different types of ctDNA liquid biopsy platforms, each with advantages and disadvantages in different clinical indications. This review provides an overview of the current and evolving use of ctDNA in CRC.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Colorectal Neoplasms; Humans; Neoplasm, Residual; Prospective Studies
PubMed: 35839443
DOI: 10.1200/JCO.21.02615 -
Nature Reviews. Molecular Cell Biology Jun 2019The metabolome, the collection of small-molecule chemical entities involved in metabolism, has traditionally been studied with the aim of identifying biomarkers in the... (Review)
Review
The metabolome, the collection of small-molecule chemical entities involved in metabolism, has traditionally been studied with the aim of identifying biomarkers in the diagnosis and prediction of disease. However, the value of metabolome analysis (metabolomics) has been redefined from a simple biomarker identification tool to a technology for the discovery of active drivers of biological processes. It is now clear that the metabolome affects cellular physiology through modulation of other 'omics' levels, including the genome, epigenome, transcriptome and proteome. In this Review, we focus on recent progress in using metabolomics to understand how the metabolome influences other omics and, by extension, to reveal the active role of metabolites in physiology and disease. This concept of utilizing metabolomics to perform activity screens to identify biologically active metabolites - which we term activity metabolomics - is already having a broad impact on biology.
Topics: Animals; Biomarkers; Humans; Metabolome; Metabolomics
PubMed: 30814649
DOI: 10.1038/s41580-019-0108-4 -
Seminars in Cell & Developmental Biology Aug 2021Quantifying biological aging is critical for understanding why aging is the primary driver of morbidity and mortality and for assessing novel therapies to counter... (Review)
Review
Quantifying biological aging is critical for understanding why aging is the primary driver of morbidity and mortality and for assessing novel therapies to counter pathological aging. In the past decade, many biomarkers relevant to brain aging have been developed using various data types and modeling techniques. Aging involves numerous interconnected processes, and thus many complementary biomarkers are needed, each capturing a different slice of aging biology. Here we present a hierarchical framework highlighting how these biomarkers are related to each other and the underlying biological processes. We review those measures most studied in the context of brain aging: epigenetic clocks, proteomic clocks, and neuroimaging age predictors. Many studies have linked these biomarkers to cognition, mental health, brain structure, and pathology during aging. We also delve into the challenges and complexities in interpreting these biomarkers and suggest areas for further innovation. Ultimately, a robust mechanistic understanding of these biomarkers will be needed to effectively intervene in the aging process to prevent and treat age-related disease.
Topics: Aged; Aged, 80 and over; Aging; Biomarkers; Brain; Humans
PubMed: 33509689
DOI: 10.1016/j.semcdb.2021.01.003 -
Physiological Research Mar 2020Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not... (Review)
Review
Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. Biomarker research has expanded greatly with the advancement of molecular research techniques. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient - exhaled breath analysis, blood cells and serum biomarkers, sputum cells and mediators and urine metabolites could be potential biomarkers of asthma bronchiale. Unfortunately, at the moment, an ideal biomarker doesn't exist and the overlap between the biomarkers is a reality. Using panels of biomarkers could improve probably the identification of asthma endotypes in the era of precision medicine.
Topics: Animals; Asthma; Biomarkers; Humans; Precision Medicine; Predictive Value of Tests; Sputum
PubMed: 32228009
DOI: 10.33549/physiolres.934398 -
Current Opinion in Clinical Nutrition... Sep 2023To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel... (Review)
Review
PURPOSE OF REVIEW
To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations.
RECENT FINDINGS
The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better 'umbrella' terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS.
SUMMARY
Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.
Topics: Humans; Irritable Bowel Syndrome; Malabsorption Syndromes; Glutens; Diet, Gluten-Free; Biomarkers; Celiac Disease
PubMed: 36942921
DOI: 10.1097/MCO.0000000000000925 -
International Journal of Molecular... Jan 2023In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction... (Review)
Review
In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25-30%) representing an aggressive subtype (Gleason score 7-10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.
Topics: Male; Humans; United States; Prostatic Neoplasms; Prostate; Prostate-Specific Antigen; Early Detection of Cancer; Biopsy; Biomarkers, Tumor
PubMed: 36768533
DOI: 10.3390/ijms24032185 -
Biochemia Medica Oct 2019The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For... (Review)
Review
The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable measure of physiological, biological age. Biomarkers should meet several criteria. For example, they have to predict the rate of aging, monitor a basic process that underlies the aging process, be able to be tested repeatedly without harming the person. In addition, biomarkers have to be indicators of biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. It is considered that the telomere length is the weak biomarker (with poor predictive accuracy), and there is currently no reliable biomarker that meets all the necessary criteria.
Topics: Aging; Biomarkers; Cellular Senescence; DNA Damage; Humans; Immune System; Oxidative Stress; Reactive Oxygen Species; Telomere Homeostasis
PubMed: 31379458
DOI: 10.11613/BM.2019.030501 -
Biochimica Et Biophysica Acta.... Sep 2021The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during... (Review)
Review
The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during inflammation. VCAM-1 expression, together with soluble VCAM-1 (sVCAM-1) induced by the shedding of VCAM-1 by metalloproteinases, have been proposed as biomarkers in immunological diseases, cancer, autoimmune myocarditis, and as predictors of mortality and morbidity in patients with chronic heart failure (HF), endothelial injury in patients with coronary artery disease, and arrhythmias. This revision aims to discuss the role of sVCAM-1 as a biomarker to predict the occurrence, development, and preservation of cardiovascular disease.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Humans; Myocarditis; Vascular Cell Adhesion Molecule-1
PubMed: 34000374
DOI: 10.1016/j.bbadis.2021.166170 -
American Journal of Physiology.... Jul 2021Intestinal permeability is an important diagnostic marker, yet its determination by established tests, which measure the urinary excretion of orally administered tracer...
Intestinal permeability is an important diagnostic marker, yet its determination by established tests, which measure the urinary excretion of orally administered tracer molecules, is time consuming and can only be performed prospectively. Here, we aim to validate proposed surrogate biomarkers, which allow measuring intestinal permeability more easily. In this cross-sectional study, we included two independent cohorts comprising nonobese (Healthy cohort, = 51) and individuals with obesity (Obesity cohort, = 27). The lactulose/mannitol (lac/man) ratio was determined in all individuals as an established marker of intestinal permeability. Furthermore, we measured six potential surrogate biomarkers, being albumin, calprotectin, and zonulin, measured in feces, as well as intestinal fatty acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP) and zonulin, measured in plasma. Correlation analyses and multiple linear regression models were conducted to assess possible associations between the established lac/man ratio and the proposed biomarkers by also evaluating a potential effect of age, body mass index (BMI), and sex. The lac/man ratio correlated with plasma LBP levels in all cohorts consistently and with the amount of fecal zonulin in overweight and obese individuals. Multiple linear regression models showed that the association between the lac/man ratio and plasma LBP was independent of age, BMI, and sex. Fecal zonulin levels were associated with the lac/man ratio as well as BMI, but not age and sex. Our data suggest plasma LBP as a promising biomarker for intestinal permeability in adults and fecal zonulin as a potential biomarker in overweight and obese individuals. This study shows that biomarkers from blood and fecal samples are associated with the cumbersome established tests of intestinal permeability throughout different cohorts. Therefore, such biomarkers could be used to assess gut barrier function in prospective cohort studies and large-scale clinical trials for which tracer-based tests may not be feasible.
Topics: Adult; Biomarkers; Cross-Sectional Studies; Fatty Acid-Binding Proteins; Female; Gastrointestinal Microbiome; Haptoglobins; Humans; Intestinal Mucosa; Male; Obesity; Permeability; Prospective Studies; Protein Precursors
PubMed: 34009040
DOI: 10.1152/ajpgi.00113.2021