TY  - JOUR
AB  - OBJECTIVES: Serum protein electrophoresis (SPE) in combination with immunotyping (IMT) is the diagnostic standard for detecting monoclonal proteins (M-proteins). However, interpretation of SPE and IMT is weakly standardized, time consuming and investigator dependent. Here, we present five machine learning (ML) approaches for automated detection of M-proteins on SPE on an unprecedented large and well-curated data set and compare the performance with that of laboratory experts. METHODS: SPE and IMT were performed in serum samples from 69,722 individuals from Norway. IMT results were used to label the samples as M-protein present (positive, n=4,273) or absent (negative n=65,449). Four feature-based ML algorithms and one convolutional neural network (CNN) were trained on 68,722 randomly selected SPE patterns to detect M-proteins. Algorithm performance was compared to that of an expert group of clinical pathologists and laboratory technicians (n=10) on a test set of 1,000 samples. RESULTS: The random forest classifier showed the best performance (F1-Score 93.2 %, accuracy 99.1 %, sensitivity 89.9 %, specificity 99.8 %, positive predictive value 96.9 %, negative predictive value 99.3 %) and outperformed the experts (F1-Score 61.2 ± 16.0 %, accuracy 89.2 ± 10.2 %, sensitivity 94.3 ± 2.8 %, specificity 88.9 ± 10.9 %, positive predictive value 47.3 ± 16.2 %, negative predictive value 99.5 ± 0.2 %) on the test set. Interestingly the performance of the RFC saturated, the CNN performance increased steadily within our training set (n=68,722). CONCLUSIONS: Feature-based ML systems are capable of automated detection of M-proteins on SPE beyond expert-level and show potential for use in the clinical laboratory.
AU  - Elfert, E.*
AU  - Kaminski, W.E.*
AU  - Matek, C.
AU  - Hoermann, G.*
AU  - Axelsen, E.W.*
AU  - Marr, C.
AU  - Piehler, A.P.*
C1  - 70843
C2  - 55950
CY  - Genthiner Strasse 13, D-10785 Berlin, Germany
TI  - Expert-level detection of M-proteins in serum protein electrophoresis using machine learning.
JO  - Clin. Chem. Lab. Med.
PB  - Walter De Gruyter Gmbh
PY  - 2024
SN  - 1434-6621
ER  - 

TY  - JOUR
AB  - Due to its high specificity, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered the gold standard in diagnostic areas such as therapeutic monitoring of immunosuppressive drugs (ISDs). However, many laboratories still rely on immunoassays for ISD quantification in a tradeoff between analytical performance and the advantages of fully automated analyzers - shorter turnaround times, greater ease of use, and 24/7 availability. The LC-MS/MS-based Thermo Scientific™ Cascadion™ SM Immunosuppressant Panel was evaluated for >6 months in the routine laboratory of a university hospital. We assessed the analytical performance of the panel and compared it to conventional LC-MS/MS as well as to immunoassays (cyclosporine A, sirolimus, tacrolimus (Siemens) and everolimus (Thermo Fisher)). In addition, both ISD panel and Cascadion analyzer were scrutinized with regards to, e.g., turnaround time, usability, and robustness. All ISDs showed high linearity and precision (CV≤6%) and a good correlation with conventional LC-MS/MS. The mean deviation to the immunoassays was 17-19% and negative for all ISDs except everolimus with a positive 19% bias. No weak points were revealed when challenging assay and system with, e.g., high haematocrit, sedimented whole blood or priority samples. The Cascadion integrated well into our 24/7 routine and could easily be operated simultaneously with several other analyzers by technical staff without LC-MS experience. The ISD panel showed excellent analytical performance and demonstrated that a fully automated LC-MS-based analysis starting from primary samples is feasible, suggesting that LC-MS could become an integral part of 24/7 diagnostics in the near future.
AU  - Hörber, S.
AU  - Peter, A.
AU  - Lehmann, R.
AU  - Hoene, M.
C1  - 60490
C2  - 49310
CY  - Genthiner Strasse 13, D-10785 Berlin, Germany
SP  - 913-920
TI  - Evaluation of the first immunosuppressive drug assay available on a fully automated LC-MS/MS-based clinical analyzer suggests a new era in laboratory medicine.
JO  - Clin. Chem. Lab. Med.
VL  - 59
IS  - 5
PB  - Walter De Gruyter Gmbh
PY  - 2020
SN  - 1434-6621
ER  - 

TY  - JOUR
AB  - Background: High sensitivity assays for the determination of cardiac troponin I (cTnI) are able to reliably measure cTnI far below the 99th percentile of healthy persons (hs-cTnI) and display sex-specific differences. There is uncertainty regarding the clinical utility of hs-cTnI in asymptomatic hemodialysis (HD) patients and if sex-specific differences also apply in this cohort.Methods: In this multicenter study we measured hs-cTnI and sensitive cTnI (s-TnI) concentrations (both on Siemens Centaur) in 215 HD patients from a predialytic sample to determine the prevalence of elevated concentrations above the 99th percentile, the association with baseline characteristics, prognostic accuracy for death, and sex-specific differences.Results: Hs-cTnI and s-cTnI concentrations were below the 99th percentile in 93% and 85% of patients with a median concentration of 12 ng/L (interquartile range 7-66) and 19 ng/L (12; 31, p < 0.0001). Hs-cTnI and s-cTnI concentrations were independently associated with age (p < 0.05) and ischemic cardiac disease (p < 0.05), but not with residual renal function. Both hs-cTnI and s-cTnI were predictors of death after median follow-up of 2.6 years with an AUC of 0.733 and 0.744, respectively (both p < 0.0001). Important sex-differences emerged for hs-cTnI, but not for s-cTnI: first, women had significantly lower hs-cTnI concentrations than men (p = 0.03); second, hs-cTnI had significantly higher prognostic accuracy for death in women than for men (AUC 0.824 vs. 0.674, p = 0.04).Conclusions: The majority of HD patients have (h)s-cTnI concentrations below the 99th percentile. High normal values are predictive of death. Hs-cTnI allows to elucidate important sex-differences in HD patients with lower concentrations and higher prognostic accuracy in women.
AU  - Artunc, F.
AU  - Haag, S.*
AU  - Friedrich, B.*
AU  - Mueller, C.*
AU  - Häring, H.-U.
AU  - Peter, A.
C1  - 55788
C2  - 46564
CY  - Genthiner Strasse 13, D-10785 Berlin, Germany
SP  - 1261-1270
TI  - Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients - evidence for sex-specific differences.
JO  - Clin. Chem. Lab. Med.
VL  - 57
IS  - 8
PB  - Walter De Gruyter Gmbh
PY  - 2019
SN  - 1434-6621
ER  - 

TY  - JOUR
AU  - Kempe-Teufel, D.
AU  - Bissinger, R.*
AU  - Qadri, S.M.*
AU  - Wagner, R.
AU  - Peter, A.
AU  - Lang, F.*
C1  - 53677
C2  - 44851
SP  - E177-E180
TI  - Cellular markers of eryptosis are altered in type 2 diabetes.
JO  - Clin. Chem. Lab. Med.
VL  - 56
IS  - 7
PY  - 2018
SN  - 1434-6621
ER  - 

TY  - JOUR
AB  - The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
AU  - Apweiler, R.*
AU  - Aslanidis, C.*
AU  - Deufel, T.*
AU  - Gerstner, A.*
AU  - Hansen, J.*
AU  - Hochstrasser, D.*
AU  - Kellner, R.*
AU  - Kubicek, M.*
AU  - Lottspeich, F.*
AU  - Maser, E.*
AU  - Mewes, H.-W.
AU  - Meyer, H.E.*
AU  - Müllner, S.*
AU  - Mutter, W.*
AU  - Neumaier, M.*
AU  - Nollau, P.*
AU  - Nothwang, HG.*
AU  - Ponten, F.*
AU  - Radbruch, A.*
AU  - Reinert, K.*
AU  - Rothe, G.*
AU  - Stockinger, H.*
AU  - Tarnok, A.*
AU  - Taussig, M.J.*
AU  - Thiel, A.*
AU  - Thiery, J.*
AU  - Ueffing, M.
AU  - Valet, G.*
AU  - Vandekerckhove, J.*
AU  - Verhuven, W.*
AU  - Wagener, C.*
AU  - Wagner, O.*
AU  - Schmitz, G.*
C1  - 2253
C2  - 26410
SP  - 724-744 
TI  - Approaching clinical proteomics: Current state and future fields of application in cellular proteomics.
JO  - Clin. Chem. Lab. Med.
VL  - 47
IS  - 6
PB  - de Gruyter
PY  - 2009
SN  - 1434-6621
ER  - 

TY  - JOUR
AB  - Background: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1b), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA-238A, IL1B-31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1b, respectively. Alleles CD14-159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. Methods: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. Results: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN*2/*2; IL1B-31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. Conclusions: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.
AU  - Petrásek, J.*
AU  - Hubácek, J.A.*
AU  - Stickel, F.*
AU  - Sperl, J.S.*
AU  - Berg, T.*
AU  - Ruf, E.*
AU  - Wichmann, H.-E.
AU  - Pfeufer, A.
AU  - Meitinger, T.
AU  - Trunecka, P.*
AU  - Spicák, J.*
AU  - Jirsa, M.*
C1  - 1010
C2  - 26133
SP  - 398-404
TI  - Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?
JO  - Clin. Chem. Lab. Med.
VL  - 47
IS  - 4
PB  - de Gruyter
PY  - 2009
SN  - 1434-6621
ER  - 

TY  - JOUR
AU  - Koch, W.*
AU  - Hoppmann, P.*
AU  - Michou, E.*
AU  - Jung, V.*
AU  - Pfeufer, A.
AU  - Müller, J.
AU  - Meitinger, T.
AU  - Schömig, A.*
AU  - Kastrati, A.*
C1  - 4296
C2  - 22770
SP  - 167-172
TI  - TaqMan assays for genotyping of single nucleotide polymorphisms present at a disease susceptibility locus on chromosome 6.
JO  - Clin. Chem. Lab. Med.
VL  - 43
PY  - 2005
SN  - 1434-6621
ER  - 

TY  - JOUR
AB  - The application of ICP emission spectroscopy for the direct determination of aluminum in blood serum was investigated and the method with all important parameters is described. The well known matrix interferences in atomic absorption spectroscopy do not exist in ICP spectroscopy, due to the very high excitation temperature of the sample of about 8000 K. It is therefore possible to perform very sensitive and reproducible measurements.
AU  - Schramel, P.
AU  - Wolf, A.
AU  - Klose, B.J.
C1  - 41492
C2  - 38404
SP  - 591-593
TI  - Direktbestimmung von Aluminium in Serumproben mittels inductively coupled plasma (ICP)-Emissionsspektralanalyse.
JO  - Clin. Chem. Lab. Med.
VL  - 18
IS  - 9
PY  - 1980
SN  - 1434-6621
ER  -