Candidate Biomarker Panels

Historically, circulating biomarkers have been defined by a single analyte that can be used to distinguish given groups of individuals with high specificity and sensitivity (positive and negative predictive values). In the last two decades, the development of high-throughput multivariate analytical platforms, such as protein and gene chips, has enabled the identification and validation of multivariate biomarkers. Due to population variation and the multitude of effects that treatment can have within a person and across the population, it is acknowledged that panels of proteins are likely to produce a biomarker that is significantly more sensitive and specific than any single protein alone [38].

In a typical biomarker discovery study performed on the CellCarta platform, hundreds of proteins are found to be significantly differentially modulated. These proteins are then prioritized into panels of 3 to 10 proteins. This process involves filtering based on several criteria, including diagnostic strength [i.e., the area under the receiver operator characteristic (ROC) curve or AUC] and linear regression to clinical factors. In particular, the panel of proteins must have a high composite AUC in addition to strong individual protein AUC scores. Biomarker panels with high discriminating power (positive and negative predictive values) can thus be composed from the individual bio-marker candidates. The number of protein candidates included in the panel jta

Figure 3 Caprion Data Report user interface. An example Data Report screenshot is shown. The upper left panel contains a summary of the proteomic data for the proteins selected by the user. The upper right panel contains several tabs that permit additional details to be displayed, including a hierarchical clustering of the peptides. The lower left panel contains search options, while the lower right panel contains several tabs that provide additional proteomic data, such as peptide intensities, differential expression, and MS/MS spectra.

Figure 3 Caprion Data Report user interface. An example Data Report screenshot is shown. The upper left panel contains a summary of the proteomic data for the proteins selected by the user. The upper right panel contains several tabs that permit additional details to be displayed, including a hierarchical clustering of the peptides. The lower left panel contains search options, while the lower right panel contains several tabs that provide additional proteomic data, such as peptide intensities, differential expression, and MS/MS spectra.

represents a trade-off between cost and risk. Although larger protein panels are more costly to verify, they are more resilient to population variability. Prioritized candidate biomarkers are then qualified and verified further using immunoassays such as enzyme-linked immunosorbent assay (ELISA) or mass spectrometry-based assays such as multiple reaction monitoring (MRM) [39,40].

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Project Management Made Easy

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