Abstract:
BACKGROUND:Multiple reaction monitoring mass spectrometry (MRM-MS) of peptides with stable isotope-labeled internal standards (SISs) is increasingly being used to develop quantitative assays for proteins in complex biological matrices. These assays can be highly precise and quantitative, but the frequent occurrence of interferences requires that MRM-MS data be manually reviewed, a time-intensive process subject to human error. We developed an algorithm that identifies inaccurate transition data based on the presence of interfering signal or inconsistent recovery among replicate samples. METHODS:The algorithm objectively evaluates MRM-MS data with 2 orthogonal approaches. First, it compares the relative product ion intensities of the analyte peptide to those of the SIS peptide and uses a t-test to determine if they are significantly different. A CV is then calculated from the ratio of the analyte peak area to the SIS peak area from the sample replicates. RESULTS:The algorithm identified problematic transitions and achieved accuracies of 94%-100%, with a sensitivity and specificity of 83%-100% for correct identification of errant transitions. The algorithm was robust when challenged with multiple types of interferences and problematic transitions. CONCLUSIONS:This algorithm for automated detection of inaccurate and imprecise transitions (AuDIT) in MRM-MS data reduces the time required for manual and subjective inspection of data, improves the overall accuracy of data analysis, and is easily implemented into the standard data-analysis work flow. AuDIT currently works with results exported from MRM-MS data-processing software packages and may be implemented as an analysis tool within such software.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Abbatiello SE,Mani DR,Keshishian H,Carr SAdoi
10.1373/clinchem.2009.138420subject
Has Abstractpub_date
2010-02-01 00:00:00pages
291-305issue
2eissn
0009-9147issn
1530-8561pii
clinchem.2009.138420journal_volume
56pub_type
杂志文章abstract:BACKGROUND:Pompe disease (PD) is the first lysosomal storage disorder to be added to the Recommended Uniform Screening Panel for newborn screening. This condition has a broad phenotypic spectrum, ranging from an infantile form (IOPD), with severe morbidity and mortality in infancy, to a late-onset form (LOPD) with vari...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2016.259036
更新日期:2017-04-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::We tested a new amylase reagent involving chromogenic substrates (Pantrak, Calbiochem-Behring) for precision, dynamic range, and susceptibility to potential interferences. Two p-nitrophenyl-alpha-maltaosides are used as substrates, which amylase cleaves to shorter-chain p-nitrophenyl maltaosides, the latter then yield...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
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abstract::We are developing a method for quantifying plasma lipoproteins by proton nuclear magnetic resonance (NMR) spectroscopy that offers advantages over existing clinical methods. We showed that the major lipoproteins have distinct NMR properties sufficient to permit their concentrations to be extracted from a computer line...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::We describe a procedure based on equilibrium dialysis that allows the simultaneous determination of free testosterone and testosterone bound to non-sex-hormone-binding globulin (non-SHBG) in plasma. After saturating SHBG with 5 alpha-dihydrotestosterone (DHT) according to a technique recently described, the percentage...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::We describe an enzyme-linked immunosorbent assay for determination of light-chain ratios for IgG, IgA, and IgM in serum. A commercial serum with known overall kappa and lambda concentrations was used as standard. To capture the respective immunoglobulins, we used antibodies to gamma, lambda and mu chains coated onto m...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Specific gravity (SG) may perform as well as creatinine (CR) correction for adjusting urinary hormone concentrations, as well as offer some advantages. We compared the two methods and applied them to US and Bangladeshi specimens to evaluate their use in different populations. METHODS:Pearson correlations be...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2004.032292
更新日期:2004-05-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1981-07-01 00:00:00
abstract:BACKGROUND:A substantial proportion of the variability in the absorption and clearance of cyclosporin A (CsA) after oral administration has been attributed to variability in liver cytochrome P-450 3A4 (CYP3A4) activity and intestinal P-glycoprotein (P-gp) concentration. A polymorphism in the CYP3A4 promoter region, ter...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::Creatine kinase (CK) isoenzymes MM, MB, and BB are located primarily in the cell cytosol, and increased CKMB in plasma is the hallmark of myocardial infarction. However, whether CK is released with reversible ischemic injury remains controversial. Here, we assessed plasma CK activity--cytosolic and mitochondrial CK--i...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::A simple computer-based screening technique has been developed for classifying human expired air components into 16 chemical classes, based on empirical formulas. The sort procedure was developed to simplify the screening of the composition of expired air samples by sorting all components into chemical classes and cla...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Use of immunoassays that do not detect endogenous digoxin-like immunoreactive factors (DLIF) in serum significantly improves the between-assay correlation of digoxin results for patients. We investigated five different immunoassay methods (Abbott, Clinical Assays, Corning, Du Pont, and Syva), measuring digoxin by all ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Prostate-specific antigen (PSA) is a valuable prostatic cancer biomarker that is now widely used for population screening, diagnosis, and monitoring of patients with prostate cancer. Despite the voluminous literature on this biomarker, relatively few reports have addressed the issue of its physiological func...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:2000-07-01 00:00:00
abstract::A monoclonal-antibody-based competitive radioimmunoassay for measuring human protein C is reported. With use of a purified protein C standard, the solid-phase assay was sensitive to less than 80 micrograms of protein C per liter. Intraassay CVs ranged from 5% to 8%; the inter-assay CV was 5.4%. Analytical recovery ave...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract:BACKGROUND:Recent studies have suggested that single-stranded DNA (ssDNA) library preparation can enrich short DNA species from the plasma of healthy individuals, cancer patients, and transplant recipients. Based on previous observations that fetal DNA molecules in the maternal plasma are shorter than maternal DNA mole...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2016.268656
更新日期:2017-05-01 00:00:00
abstract::This communication describes and evaluates an improved routine methodology for quantitating clinical proteinuria. Based on investigations of Piscator and of Savory et al., a modified Tsuchiya's reagent (ethanolic HCI-phosphotungstic acid) is used to precipitate proteins at 56 degrees C, followed by biuret spectrophoto...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1975-03-01 00:00:00
abstract::The topic of quality control often evokes prolific discussion among those whose business is its administration. Reliable methods for identifying mistakes must be developed in both the manufacture and use of test devices. Unit test devices are uncomplicated to run and provide quick results in a world where speed and si...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1997-05-01 00:00:00
abstract::The kidney and its response to the antidiuretic hormone (ADH) are the principal protective mechanisms necessary to maintain a normal plasma tonicity (osmolality). Hence, determination of the response of the ADH-renal axis to an abnormal plasma tonicity is an important step to understanding water homeostasis. Determina...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone that exists in multiple forms. Immunoassays commonly used in clinical laboratories measure intact hCG, total beta hCG (intact hCG + hCG free beta-subunit), and/or hCG free beta-subunit. Measurement of serum concentrations of hCG is us...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2007.098822
更新日期:2008-04-01 00:00:00
abstract::We describe the process of certification for a gamma-glutamyltransferase reference material (CRM no. 319). Fifteen laboratories participated to this interlaboratory evaluation. All steps of the measurements were controlled in an effort to locate potential sources of variations. In particular, the exclusion of some dat...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::In photometry, where both the product formed and one or several reactants absorb light at the same wavelength, the absorbance of the "blank" of the sample at the end of the reaction may be less than that measured at the beginning of the reaction, because of consumption of reactant(s). The blank correction factor for t...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitop...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::We describe a rapid polarization fluoroimmunoassay for screening for the presence of barbiturates in urine. The single reagent is prepared by pre-mixing antiserum with a fluorescein-labeled barbiturate derivative as tracer. Use of a mixture of two sheep antisera, raised against different barbiturate immunogens, result...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Detection and characterization of small IgM paraproteins by immunoelectrophoresis are often difficult because of (a) slow diffusion of the macromolecular immunoglobulin, and (b) the obscuring of the light chain, especially kappa, by the light chains of background polyclonal immunoglobulin (the "umbrella effect"). Vari...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::We determined the urinary excretion of 5-fluorouracil (5FU) and its metabolites during six days of chemotherapy, using the non-invasive approach of 19F nuclear magnetic resonance. With this method, which requires no labeled drug, one can study the biological sample directly and simultaneously identify and quantify all...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::We describe a new, specific, quantitative method for fecal blood, based on conversion of nonfluorescing heme to fluorescing porphyrins, that obviates serious deficiencies inherent in currently used tests. A two-reagent system is used to determine the two hemoglobin-related fractions that are found in feces. The hot ci...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
abstract:BACKGROUND:The analytical and clinical performance of homogeneous LDL-cholesterol assays has been reported, but their reactions with subfractions of LDL and VLDL have not been described in detail. METHODS:We evaluated reaction selectivity of two homogeneous LDL-cholesterol assays, LDLk (Kyowa Medex) and LDLd (Daiichi ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Serum concentrations of apolipoprotein (apo) B and apo A-I were measured from 1985-1996 in a Swedish population sample of 83 112 males and 64 464 females, ages <20 to >80 years, using an automated immunoturbidimetric method calibrated against fresh pools of human serum and commercial calibrators. All values were recal...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::The values of apolipoproteins (apo) A-I and B were determined in a population sample of hospital outpatients with a standardized method to verify if the cutpoints calculated in a cross-sectional study in the US are usable with other populations. We also tested the apolipoproteins' ability to discriminate between healt...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00