scholarly journals Diagnostic Biomarkers: Are We Moving from Discovery to Clinical Application?

2018 ◽  
Vol 64 (11) ◽  
pp. 1657-1667 ◽  
Author(s):  
Lucy A Parker ◽  
Elisa Chilet-Rosell ◽  
Ildefonso Hernández-Aguado ◽  
María Pastor-Valero ◽  
Sonia Gea ◽  
...  
Keyword(s):  
Clinical Application ◽  
Diagnostic Tests ◽  
Biomarker Discovery ◽  
Diagnostic Value ◽  
Original Research ◽  
Technical Improvement ◽  
Diagnostic Biomarkers ◽  
Diagnostic Studies ◽  
Research Investment ◽  
Biomedical Journals

Abstract BACKGROUND Despite considerable research investment, moving from biomarker discovery to clinical application has presented unique challenges. We aimed to evaluate progress toward clinical application of a sample of molecular- and “omics”-based diagnostic tests over a 10-year period. METHODS We used Scopus to locate studies, published before the December 31, 2016, citing 107 original-research articles published in 2006 that assessed the diagnostic value of a molecular- or “omics”-based test. We identified diagnostic studies of the same test and disease and determined whether the article represented progress in the validation of the molecular test. We classified the types of progress: (a) clinical validation (measuring diagnostic accuracy in a series of patients similar to the population in which the test will be used in practice), (b) technical improvement, (c) extended diagnostic application (modification of the diagnostic question attended initially by the test), (d) economic evaluation, or (e) clinical use or implementation. RESULTS In the 10-year period analyzed, 4257 articles cited the 107 diagnostic studies; 118 (2.8%) were diagnostic studies of the same test, and of these papers, 25 (21.2%) did not constitute progress toward validation of the test for use in clinical practice (potential research waste). Of the 107 molecular- or “omics”-based tests described in 2006, only 28 (26.2%) appeared to have made progress toward clinical application. Only 4 (9.1%) of 44 proteomics-based tests had made progress toward clinical application. CONCLUSIONS Articles evaluating molecular- or “omics”-based diagnostic tests are numerous in biomedical journals. Few tests have made progress toward clinical application in the 10 years following their discovery.

scholarly journals Overinterpretation of Clinical Applicability in Molecular Diagnostic Research

2009 ◽  
Vol 55 (4) ◽  
pp. 786-794 ◽  
Author(s):  
Blanca Lumbreras ◽  
Lucy A Parker ◽  
Miquel Porta ◽  
Marina Pollán ◽  
John P A Ioannidis ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Diagnostic Value ◽  
Molecular Techniques ◽  
Impact Factors ◽  
Molecular Diagnostic ◽  
Original Research ◽  
Clinical Applicability ◽  
Diagnostic Research

Abstract Background: We evaluated whether articles on molecular diagnostic tests interpret appropriately the clinical applicability of their results. Methods: We selected original-research articles published in 2006 that addressed the diagnostic value of a molecular test. We defined overinterpretation of clinical applicability by means of prespecified rules that evaluated study design, conclusions regarding applicability, presence of statements suggesting the need for further clinical evaluation of the test, and diagnostic accuracy. Two reviewers independently evaluated the articles; consensus was reached after discussion and arbitration by a third reviewer. Results: Of 108 articles included in the study, 82 (76%) used a design that used healthy controls or alternative-diagnosis controls, only 15 (11%) addressed a clinically relevant population similar to that in which the test might be applied in practice, 104 articles (96%) made definitely favorable or promising statements regarding clinical applicability, and 61 (56%) of the articles apparently overinterpreted the clinical applicability of their findings. Articles published in journals with higher impact factors were more likely to overinterpret their results than those with lower impact factors (adjusted odds ratio, 1.71 per impact factor quartile; 95% CI, 1.09–2.69; P = 0.020). Overinterpretation was more common when authors were based in laboratories than in clinical settings (adjusted odds ratio, 18.7; 95% CI, 1.41–249; P = 0.036). Conclusions: Although expectations are high for new diagnostic tests based on molecular techniques, the majority of published research has involved preclinical phases of research. Overinterpretation of the clinical applicability of findings for new molecular diagnostic tests is common.

Cancer Biomarker Discovery for Precision Medicine: New Progress

2020 ◽  
Vol 26 (42) ◽  
pp. 7655-7671 ◽  
Author(s):  
Jinfeng Zou ◽  
Edwin Wang
Keyword(s):  
Precision Medicine ◽  
Cancer Patients ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Biomarker Discovery ◽  
Deep Understanding ◽  
Genetic Mutation ◽  
Data Driven ◽  
Novel Approaches ◽  
Functional Biomarkers

Background: Precision medicine puts forward customized healthcare for cancer patients. An important way to accomplish this task is to stratify patients into those who may respond to a treatment and those who may not. For this purpose, diagnostic and prognostic biomarkers have been pursued. Objective: This review focuses on novel approaches and concepts of exploring biomarker discovery under the circumstances that technologies are developed, and data are accumulated for precision medicine. Results: The traditional mechanism-driven functional biomarkers have the advantage of actionable insights, while data-driven computational biomarkers can fulfill more needs, especially with tremendous data on the molecules of different layers (e.g. genetic mutation, mRNA, protein etc.) which are accumulated based on a plenty of technologies. Besides, the technology-driven liquid biopsy biomarker is very promising to improve patients’ survival. The developments of biomarker discovery on these aspects are promoting the understanding of cancer, helping the stratification of patients and improving patients’ survival. Conclusion: Current developments on mechanisms-, data- and technology-driven biomarker discovery are achieving the aim of precision medicine and promoting the clinical application of biomarkers. Meanwhile, the complexity of cancer requires more effective biomarkers, which could be accomplished by a comprehensive integration of multiple types of biomarkers together with a deep understanding of cancer.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

scholarly journals HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhixin Wu ◽  
Yinxian Wen ◽  
Guanlan Fan ◽  
Hangyuan He ◽  
Siqi Zhou ◽  
...  
Keyword(s):  
Femoral Head ◽  
Roc Curve ◽  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Overlapping Genes ◽  
Hub Genes ◽  
Diagnostic Biomarkers ◽  
Key Genes

Abstract Background Steroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling bone disease. This study aims to reveal novel diagnostic biomarkers of SONFH. Methods The GSE123568 dataset based on peripheral blood samples from 10 healthy individuals and 30 SONFH patients was used for weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. The genes in the module related to SONFH and the DEGs were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Genes with |gene significance| > 0.7 and |module membership| > 0.8 were selected as hub genes in modules. The DEGs with the degree of connectivity ≥5 were chosen as hub genes in DEGs. Subsequently, the overlapping genes of hub genes in modules and hub genes in DEGs were selected as key genes for SONFH. And then, the key genes were verified in another dataset, and the diagnostic value of key genes was evaluated by receiver operating characteristic (ROC) curve. Results Nine gene co-expression modules were constructed via WGCNA. The brown module with 1258 genes was most significantly correlated with SONFH and was identified as the key module for SONFH. The results of functional enrichment analysis showed that the genes in the key module were mainly enriched in the inflammatory response, apoptotic process and osteoclast differentiation. A total of 91 genes were identified as hub genes in the key module. Besides, 145 DEGs were identified by DEGs screening and 26 genes were identified as hub genes of DEGs. Overlapping genes of hub genes in the key module and hub genes in DEGs, including RHAG, RNF14, HEMGN, and SLC2A1, were further selected as key genes for SONFH. The diagnostic value of these key genes for SONFH was confirmed by ROC curve. The validation results of these key genes in GSE26316 dataset showed that only HEMGN and SLC2A1 were downregulated in the SONFH group, suggesting that they were more likely to be diagnostic biomarkers of SOFNH than RHAG and RNF14. Conclusions Our study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH.

Diagnostic tests in child poisoning

1968 ◽  
Vol 6 (26) ◽  
pp. 103-104
Keyword(s):  
Clinical Response ◽  
Diagnostic Tests ◽  
Toxic Substance ◽  
Diagnostic Value ◽  
England And Wales ◽  
Unexplained Symptoms ◽  
Seriously Ill ◽  
Symptoms And Signs

Each year about 200 children under the age of fifteen die in England and Wales from poisoning.1 2 Poisoning must always be considered when a child shows unexplained symptoms and signs, is in coma or is seriously ill. The nature of the toxic substance is frequently not known, and sometimes an antidote giving a rapid clinical response is of diagnostic value. This article discusses only the diagnostic help that certain drugs can give; it does not summarise treatment.

Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis

2018 ◽  
Vol 103 (9) ◽  
pp. 1296-1300 ◽  
Author(s):  
Fahriye Groen-Hakan ◽  
Laura Eurelings ◽  
Aniki Rothova ◽  
Jan van Laar
Keyword(s):  
Diagnostic Tests ◽  
Medical Center ◽  
Age At Onset ◽  
Diagnostic Value ◽  
Youden Index ◽  
First Episode ◽  
Operating Characteristics ◽  
Non Invasive ◽  
Erasmus Medical ◽  
Uveitis Attack

Background/aimsThe diagnostic properties of conventional diagnostic tests (ACE and chest radiography) for sarcoidosis-associated uveitis are not ideal. The diagnostic value of lymphopaenia for sarcoidosis-associated uveitis is investigated.MethodsA retrospective study of 191 consecutive patients with a first uveitis episode visiting the ophthalmology department (Erasmus Medical Center, Rotterdam, The Netherlands). Receiver operating characteristics (ROC) analysis was performed and compared with known ROC values from literature of conventional diagnostic tests for sarcoidosis-associated uveitis. An ideal cut-off was determined for lymphopaenia by calculation of the highest Youden index.ResultsOut of all patients with first uveitis attack, 32/191 or 17% were subsequently diagnosed with biopsy-proven or radiological diagnosis of sarcoidosis. Lymphopaenia (<1.5×109/L) was significantly more often observed in patients with sarcoidosis-associated uveitis compared with patients with non-sarcoidosis-associated uveitis (p<0.05). The sensitivity and specificity of lymphopaenia was 75 % and 77 %, respectively. The optimal cut-off for lymphopaenia for diagnosing sarcoidosis-associated uveitis was 1.47 ×109/L. Lymphopaenia resulted in a 12.0 (95% CI 4.7 to 30.5 fold risk for having sarcoidosis, corrected for sex, race and age at onset of uveitis in patients with a first uveitis attack.ConclusionLymphopaenia is a non-invasive and useful marker for diagnosing sarcoidosis-associated uveitis.

scholarly journals PubMed Central: An Essential Resource for Information Professionals and Researchers

2013 ◽  
Vol 8 (2) ◽  
pp. 261
Author(s):  
Joanne L. Jordan
Keyword(s):  
Biomedical Research ◽  
Selection Criteria ◽  
Original Research ◽  
National Library ◽  
Electronic Journals ◽  
Pubmed Central ◽  
Biomedical Journals ◽  
The Future ◽  
Subject Areas ◽  
The Subject

Objective – A review of the journals containing research listed in PubMed Central (PMC), but not selected for inclusion in the National Library of Medicine (NLM) collection. The authors identified reasons why journals had not been included in the collection and if any met the NLM selection criteria and were appropriate for inclusion. Design – Descriptive study. Setting – National Library of Medicine, United States. Subjects – 571 journals that were not included in the NLM collection but had research articles in PMC. Methods – In October 2009, a report was produced from the NLM library system listing journals tagged as having articles in PMC and not being in the NLM collection. Information was gathered on the journals identified and these were checked against the Collection Development Manual of the NLM and the NLM checklist used for selecting electronic journals. The reason for non-selection of the journal was recorded and the subject category, according to the Library of Congress Classification, was noted. Recorded reasons why journals were not selected: • Less than 15% of articles were within scope of NLM collection • Not enough articles published • Coverage (lacking original research or not for a scholarly audience) • Insufficient information to determine reason For journals where the criteria seemed to be met, the decision on selection to the NLM collection was reviewed. Main Results – The authors identified 571 journals that had articles in PMC but did not meet the criteria for inclusion in the NLM journal collection. The majority of these journals (73%) were outside the NLM scope and a further 10% had not published a sufficient number of articles to be considered. A further 3% were assessed as not intended for a scholarly audience or lacked original research and another 3% could not be reviewed due to lack of information available. There were 65 journals (11%) that were referred for further review as the selection criteria seemed to be met and 11 of these journals have subsequently been added to the NLM collection. This is in relation to 482 new print and electronic journals in total that were added to the NLM collection in 2009. However, only 369 of the 571 journals (65%) had one or more articles included in PMC; of these, 238 had one article and 33 had more than four articles in the archive. The reason that some journals had no articles in PMC at the time of this review was due to the time it takes to process new articles and embargos set by the publishers that restrict immediate listing on open access databases such as PMC. A number of these journals may also be new and may not have had a sufficient number of articles or enough information available to be able to include them in the NLM collection. To add context, the authors state that PMC contained over 115,000 NIH-funded articles by the end of November 2010. The subject areas these non-selected journals were classified under included Engineering (15%); Medicine (14%); Mathematics (10%); Chemistry (10%); and Computer Science (9%). Library Science was assigned to 2% of the journals. The Medicine journals were more likely than those in the other subject areas to be new journals without sufficient articles to be included in the NLM collection. Conclusion – When the journal title is out of the scope of the NLM collection, an individual article in that journal can still be included in PMC. This provides a solution to the problem of how to collect biomedical research that is not published in biomedical journals. This may be more important in the future as the field becomes more interdisciplinary. This also provides a useful resource for libraries and researchers searching for full-text biomedical articles. The authors conclude that analyzing the articles from the journals not selected for inclusion in the NLM collection will provide helpful information about the types of biomedical research being published in non-biomedical journals. This will highlight particular areas the NLM should pay attention to in the future.

Validation of an exome and transcriptome based diagnostic platform enabling clinical cancer therapy selection and emerging composite biomarkers for immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15583-e15583
Author(s):  
Juan-Sebstian Saldivar ◽  
Jason Harris ◽  
Sejal Desai ◽  
Erin Ayash ◽  
Prateek Tandon ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
High Sensitivity ◽  
Cancer Genes ◽  
Patient Response ◽  
Diagnostic Biomarkers ◽  
Dna And Rna ◽  
Clinical Biomarkers ◽  
Whole Exome ◽  
Ffpe Samples ◽  
Small Set

e15583 Background: While immunotherapy has become a pillar of cancer treatment, diagnostic biomarkers that consistently predict patient response to these therapies have remained elusive. There is an increasing need for the development of integrative, composite biomarkers that can model the complex biology driving response and/or resistance to immunotherapy more effectively than existing single-analyte approaches. However, the majority of current cancer diagnostic panels, with their focus on a small set of genes, provide limited ability to support these emerging advanced biomarkers. Methods: To address these limitations, we developed and validated NeXT Dx, a comprehensive enhanced exome and transcriptome based diagnostic platform designed to simultaneously characterize tumor and immune genomics from a single limited FFPE sample. To achieve higher accuracy and sensitivity for an exome scale diagnostic platform, we developed an augmented exome assay that improves uniformity of coverage across all ~20,000 genes, including boosted coverage of 248 clinically-relevant cancer genes. We validated this assay using genomic DNA and RNA extracted from tumor-derived cell-lines, constructs, clinical FFPE samples, and proficiency testing samples. The assay utilizes > = 25ng of co-extracted DNA and RNA which were sequenced using Illumina NovaSeq instruments at our CAP-accredited, CLIA-certified laboratory. Additional assay enhancements for HLA, immune repertoire, and oncoviruses were designed to further optimize the platform for immunotherapy biomarker discovery applications. Results: Validation of NeXT Dx demonstrated a performance of 99.5% sensitivity and 99.8% positive predictive value (PPV) for SNVs with > = 5% AF; 98.7% sensitivity and 97.4% PPV for indels with > = 10% AF; 97.2% sensitivity and 94.6% PPV for CNAs in samples with > = 30% tumor content; 94.9% sensitivity and 94.9% PPV for fusions; and a 2.1% error rate for MSI classification. TMB was calculated using gold-standard whole exome data from SNVs and indels. Typical median coverage depth was > 1,000X for 248 clinically-relevant genes, ~300X for the remaining (whole exome) footprint. Conclusions: With NeXT Dx, we demonstrate a exome/transcriptome scale diagnostic platform that can detect current clinical biomarkers with high sensitivity as well as support emerging, advanced biomarkers that integrate across both tumor and immune features.

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