Abstract：
BACKGROUND:Plasma amino acid (PAA) profiles are used in routine clinical practice for the diagnosis and monitoring of inherited disorders of amino acid metabolism, organic acidemias, and urea cycle defects. Interpretation of PAA profiles is complex and requires substantial training and expertise to perform. Given previous demonstrations of the ability of machine learning (ML) algorithms to interpret complex clinical biochemistry data, we sought to determine if ML-derived classifiers could interpret PAA profiles with high predictive performance. METHODS:We collected PAA profiling data routinely performed within a clinical biochemistry laboratory (2084 profiles) and developed decision support classifiers with several ML algorithms. We tested the generalization performance of each classifier using a nested cross-validation (CV) procedure and examined the effect of various subsampling, feature selection, and ensemble learning strategies. RESULTS:The classifiers demonstrated excellent predictive performance, with the 3 ML algorithms tested producing comparable results. The best-performing ensemble binary classifier achieved a mean precision-recall (PR) AUC of 0.957 (95% CI 0.952, 0.962) and the best-performing ensemble multiclass classifier achieved a mean F4 score of 0.788 (0.773, 0.803). CONCLUSIONS:This work builds upon previous demonstrations of the utility of ML-derived decision support tools in clinical biochemistry laboratories. Our findings suggest that, pending additional validation studies, such tools could potentially be used in routine clinical practice to streamline and aid the interpretation of PAA profiles. This would be particularly useful in laboratories with limited resources and large workloads. We provide the necessary code for other laboratories to develop their own decision support tools.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Wilkes EH,Emmett E,Beltran L,Woodward GM,Carling RSdoi
10.1093/clinchem/hvaa134subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1210-1218issue
9eissn
0009-9147issn
1530-8561pii
5900235journal_volume
66pub_type
杂志文章abstract：:We review the present knowledge of telomeres and telomerase with special attention to their role in cell proliferation, cellular senescence, and human aging. We summarize the functional aspects of telomerase in cancer, as well as its role as a useful diagnostic and prognostic tumor marker, and discuss possible approac...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1997-05-01 00:00:00
abstract：BACKGROUND:Gas6 is a vitamin K-dependent antiapoptotic protein that has been implicated in cardiovascular pathophysiology. We report the development and validation of an ELISA for Gas6, and the variation of plasma Gas6 with hormonal status in a study designed to evaluate the effect of oral contraception on plasma marke...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2007.089102
更新日期：2007-10-01 00:00:00
abstract：:Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with o...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:The accuracy of estimates of blood-alcohol concentration based on measurements of breath-alcohol concentration in a randomly selected subject by a random quantitative evidential breath-alcohol analyzer is evaluated with respect to the breath analyzer itself, its calibration, and the biological variables of the subject...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:We determined fluoxetine (Prozac) and its major metabolite norfluoxetine in plasma by liquid chromatography with fluorescence detection. After liquid-liquid extraction from 1 mL of plasma, the extract was derivatized at room temperature with dansyl chloride, and the highly fluorescent derivatives were chromatographed ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:Brain proteins extractable with distilled water or 9 mol/L urea were subjected to two-dimensional gel electrophoresis. They are examined in relation to the identification of actin, tubulin, neurofilament proteins, glial fibrillary acidic protein; proteins of human embryonic neocortex, synaptosomes, myelin, and plasma;...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1982-04-01 00:00:00
abstract：:We describe a micro-scale method for determining serum theophylline. The chromatography system includes a muBondapack C18 column and acetonitrile, 70 ml/liter of sodium acetate buffer (10 mmol/liter, ph 4.0) as the mobile phase. Test serum or plasma, 30 mul, is mixed with an equal quantity of a solution containing the...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1977-03-01 00:00:00
abstract：BACKGROUND:Concerns exist regarding how the 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is determined and whether it should be derived from normal healthy individuals. CONTENT:The 99th percentile URL of cTn is an important criterion to standardize the diagnosis of myocardial infarction (MI) f...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1093/clinchem/hvaa158
更新日期：2020-09-01 00:00:00
abstract：:We report an easy, rapid method for quantifying bone isoenzyme of alkaline phosphatase (EC 3.1.3.1., ALP) in serum. The original method described by Rosalki and Ying Foo (Clin Chem 1984;30:1182-6) was somewhat simplified. In contrast to their results, we found that bone ALP is precipitated quantitatively by wheat-germ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:We measured advanced glycosylation end products in the mesenteric artery of 37 patients (ages 29-82 years), 34 of whom were nondiabetic. Samples of arterial tissue were obtained during bowel resectioning. Advanced glycosylation end products were measured as collagen-linked fluorescence (excitation wavelength 370 nm, e...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:This simple polarization fluoroimmunoassay for detection of amphetamine in urine involves the use of a single reagent: suitably diluted antiserum plus fluorescein-labeled amphetamine as tracer. To this, one adds 10 microL of urine, incubates for a few minutes at room temperature, and measures the fluorescence polariza...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：BACKGROUND:Cardiac troponins are associated with cardiovascular risk in the general population, but whether temporal changes in cardiac troponin I provide independent prognostic information remains uncertain. Using a large community-based cohort with follow-up close to the present day, we aimed to investigate the assoc...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2018.301069
更新日期：2019-07-01 00:00:00
abstract：:We developed an automated method for measurement of alpha-amylase isoenzymes in serum by a single kinetic assay (SKA) and a double kinetic assay (DKA) with 2-chloro-4-nitrophenyl-6(5)-azido-6(5)-deoxy-beta-maltopentaoside as a substrate and 6(3)-deoxymaltotriose (DOG3) as a novel selective amylase inhibitor. DOG3 show...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:We have developed and validated simple, rapid immunoassays to measure concentrations of albumin in urine ranging from 5 to 200 mg/L. We use antiserum to human albumin, raised in sheep, and we separate the antibody-bound and free fractions of albumin by using a second antiserum, produced in donkeys, against the Fc frag...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1986-07-01 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
abstract：:Serum amyloid A (SAA), a sensitive acute-phase protein, is the precursor of AA fibrils in reactive amyloidosis. However, SAA is poorly immunogenic, and development and standardization of immunoassays of this protein have been difficult. We established an automated polyclonal/monoclonal microparticle capture enzyme imm...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:This new assay procedure for diaphorase eliminates problems of high blank rates and nonlinear kinetics associated with other methods. The dye thiazolyl blue tetrazolium bromide is reduced in the presence of NADH and diaphorase to yield a colored formazan, which as maximum absorbance at 560 nm. ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1979-12-01 00:00:00
abstract：:Phenobarbital and phenytoin are extracted and concentrated in a single step, without solvent evaporation, followed by on-column methylation and gas-chromatographic quanitation. A similar extraction step for the assay of theophylline by high-pressure liquid chromatography is described. The extraction step can be comple...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1978-09-01 00:00:00
abstract：:The main developments in the "ligand assay" field in which I have been involved are traced. These include the original development of "first generation" competitive assays relying on radiolabeled analyte markers; the development of the first "second generation", noncompetitive (ultrasensitive) methods, which rely on t...
journal_title：Clinical chemistry
pub_type： 历史文章,杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:In the diagnosis of chronic (as opposed to acute) liver diseases, combinations of indicators are needed to improve specificity. Alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2) activity in serum reportedly is a very sensitive indicator of intrahepatic cholestasis and biliary obstruction; it is also...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:Two hundred patients with liver disease were re-studied after six to eight years. The initial routine diagnosis (mainly based on morphological criteria) was confirmed in almost 80% of cases of chronic liver disease. In chronic active hepatitis, agreement was found in 86%. An alternative classification based on cluster...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:Cerebrospinal fluid (CSF) from uninfected patients and from patients with bacterial and viral meningitis was analyzed by gas-liquid chromatography, with use of a flame ionization detector, and by gas chromatography-mass spectrometry. The resulting profiles were consistent and reproducible. Hydroxy acids were the compo...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：BACKGROUND:Spurious increases in serum troponins, especially troponin T, have been reported in patients with and without acute myocardial syndromes. METHODS:We studied 78 autopsied patients without clinical myocardial infarction (MI) and correlated histologic cardiac findings with antemortem serum creatine kinase (CK)...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：BACKGROUND:In the workup of patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC), detection of loss of heterozygosity (LOH) could help pinpoint the mismatch-repair (MMR) gene carrying the germline mutation, but analysis of microsatellite markers has proved unreliable for this purpose. We developed ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2008.108902
更新日期：2008-11-01 00:00:00
abstract：:I evaluated use of the fluorescence polarization technique to measure neocarzinostatin, a proteinaceous antitumor antibiotic, and its antibody, in serum. The antigen (neocarzinostatin), labeled with fluorescein isothiocyanate, was allowed to interact with its antibody in a cuvet, in the instrument, yielding an increas...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1978-12-01 00:00:00
abstract：:We evaluated the EMIT (enzyme-multiplied immuno technique) and FPIA (fluorescence polarization immunoassay) urine screening systems for detection of benzodiazepine intake. Healthy male volunteers were given single oral therapeutic doses of alprazolam (2 mg), chlordiazepoxide (25 mg), flunitrazepam (1 mg), lorazepam (3...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：BACKGROUND:C-peptide is a marker of insulin secretion in diabetic patients. We assessed within- and between-laboratory imprecision of C-peptide assays and determined whether serum calibrators with values assigned by mass spectrometry could be used to harmonize C-peptide results. METHODS:We sent 40 different serum samp...
journal_title：Clinical chemistry
pub_type： 杂志文章,多中心研究
doi：10.1373/clinchem.2007.101287
更新日期：2008-06-01 00:00:00
abstract：:In this method for separating glycosylated from nonglycosylated hemoglobin in blood by electrophoresis on cellulose acetate membranes, we exploit the affinity of low-molecular-mass dextran sulfate for the nonglycosylated fraction, which increases the mobility of the latter relative to that of glycosylated hemoglobin. ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:We studied the pattern of acute-phase proteins (orosomucoid, C-reactive protein, and haptoglobin) in hepatocellular deficiency due to chronic alcohol consumption, characterized by a decrease in serum transferrin concentration. We found that their patterns could vary independently of hepatocellular deficiency, but depe...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：BACKGROUND:Published literature was systematically reviewed to determine the diagnostic accuracy of new protein markers of acute coronary syndromes (ACS) in symptomatic outpatients at low risk of ACS and related complications comparable to patients evaluated in emergency department chest pain units. METHODS:Studies we...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：10.1373/clinchem.2005.052456
更新日期：2005-11-01 00:00:00
