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  1. Article ; Online: rxCOV is a quantitative metric for assessing immunoassay analyte fidelity.

    Brand, Rhonda M / Pitlor, Danielle / Metter, E Jeffrey / Dudley, Beth / Karloski, Eve / Zyhowski, Ashley / Brand, Randall E / Uttam, Shikhar

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 88

    Abstract: Immunoassay based bioanalytical measurements are widely used in a variety of biomedical research and clinical settings. In these settings they are assumed to faithfully represent the experimental conditions being tested and the sample groups being ... ...

    Abstract Immunoassay based bioanalytical measurements are widely used in a variety of biomedical research and clinical settings. In these settings they are assumed to faithfully represent the experimental conditions being tested and the sample groups being compared. Although significant technical advances have been made in improving sensitivity and quality of the measurements, currently no metrics exist that objectively quantify the fidelity of the measured analytes with respect to noise associated with the specific assay. Here we introduce ratio of cross-coefficient-of-variation (rxCOV), a fidelity metric for objectively assessing immunoassay analyte measurement quality when comparing its differential expression between different sample groups or experimental conditions. We derive the metric from first principles and establish its feasibility and applicability using simulated and experimental data. We show that rxCOV assesses fidelity independent of statistical significance, and importantly, identifies when latter is meaningful. We also discuss its importance in the context of averaging experimental replicates for increasing signal to noise ratio. Finally, we demonstrate its application in a Lynch Syndrome case study. We conclude by discussing its applicability to multiplexed immunoassays, other biosensing assays, and to paired and unpaired data. We anticipate rxCOV to be adopted as a simple and easy-to-use fidelity metric for performing robust and reproducible biomedical research.
    MeSH term(s) Immunoassay/methods ; Signal-To-Noise Ratio
    Language English
    Publishing date 2023-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-27309-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Immune Microenvironment Profiling of Normal Appearing Colorectal Mucosa Biopsied Over Repeat Patient Visits Reproduciably Separates Lynch Syndrome Patients Based on Their History of Colon Cancer.

    Brand, Rhonda M / Dudley, Beth / Karloski, Eve / Zyhowski, Ashley / Raphael, Rebecca / Pitlor, Danielle / Metter, E Jeffrey / Pai, Reet / Lee, Kenneth / Brand, Randall E / Uttam, Shikhar

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients ... ...

    Abstract Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients.
    Methods: Normal-appearing colorectal tissue biopsies were obtained during repeat surveillance colonoscopies of LS patients with and without a history of CRC, healthy controls (HC), and patients with a history of sporadic CRC. Biopsies were cultured in an
    Results: Our study demonstrated that cytokine based local immune microenvironment profiling was reproducible over repeat visits and sensitive to patient LS-status and CRC history. Furthermore, we identified sets of biomarkers whose differential expression was predictive of LS-status in patients when compared to sporadic CRC patients and in identifying those LS patients with or without a history of CRC. Enrichment analysis based on these biomarkers revealed an LS and CRC status dependent constitutive inflammatory state of the normal appearing colonic mucosa.
    Discussion: This prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort of LS patients over multiple visits.
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.03.23286594
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Immune microenvironment profiling of normal appearing colorectal mucosa biopsied over repeat patient visits reproducibly separates lynch syndrome patients based on their history of colon cancer.

    Brand, Rhonda M / Dudley, Beth / Karloski, Eve / Zyhowski, Ashley / Raphael, Rebecca / Pitlor, Danielle / Metter, E Jeffrey / Pai, Reet / Lee, Kenneth / Brand, Randall E / Uttam, Shikhar

    Frontiers in oncology

    2023  Volume 13, Page(s) 1174831

    Abstract: Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients ... ...

    Abstract Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients.
    Methods: Normal-appearing colorectal tissue biopsies were obtained during repeat surveillance colonoscopies of LS patients with and without a history of CRC, healthy controls (HC), and patients with a history of sporadic CRC. Biopsies were cultured in an
    Results: Our study demonstrated that cytokine based local immune microenvironment profiling was reproducible over repeat visits and sensitive to patient LS-status and CRC history. Furthermore, we identified sets of cytokines whose differential expression was predictive of LS-status in patients when compared to sporadic CRC patients and in identifying those LS patients with or without a history of CRC. Enrichment analysis based on these biomarkers revealed an LS and CRC status dependent constitutive inflammatory state of the normal appearing colonic mucosa.
    Discussion: This prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests the existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort of LS patients over multiple visits.
    Language English
    Publishing date 2023-08-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1174831
    Database MEDical Literature Analysis and Retrieval System OnLINE

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