TY  - JOUR
AB  - Purpose: Embryo-maternal signaling during the establishment of pregnancy in horses remains one of the biggest mysteries in large animal physiology. Early pregnancy loss represents a major source of economic loss to the breeding industry. This study aimed to investigate the systemic changes associated with early pregnancy by mapping the proteome of blood plasma at 14 days in pregnant and non-pregnant mares. Experimental Design: Plasma proteomes were analysed in commercially bred pregnant (n = 17) and non-pregnant (n = 17) Thoroughbred mares at 14 days after ovulation, using high-resolution mass spectrometry. Day 14 histotroph and yolk sac fluid were also profiled and datasets were integrated through pathway analysis. Results: We identified 229 total protein IDs, with 12 increased and 10 decreased significantly in pregnant versus non-pregnant plasma. To gain functional insight, these data were aligned with proteomes of 14-day pregnant mare uterine fluid (n = 4; 1358 IDs) and conceptus fluid (soluble proteins within the yolk sac fluid; n = 4; 1152 IDs), and further interrogated using gene ontology databases and pathway analysis. Conclusions and Clinical Relevance: These analyses identified consistent systemic changes in the mare's proteome that indicate a profound and specific immune response to early pregnancy, which appears to precede the systemic endocrine response to pregnancy. Integrated pathway analysis suggests that embryo-maternal interactions in early pregnancy may mimic elements of the virus-host interaction to modulate the maternal immune response. Transthyretin (TTR) and uteroglobin (SCGB1A1) were respectively down- and upregulated in plasma while also present in uterine fluid, and are proposed to be key proteins in early pregnancy establishment. These findings contribute significantly to our knowledge of early pregnancy in the mare and identify potential new avenues for developing clinical approaches to reduce early embryo loss.
AU  - Perera, T.R.W.*
AU  - de Ruijter-Villani, M.*
AU  - Gibb, Z.*
AU  - Nixon, B.*
AU  - Sheridan, A.R.*
AU  - Stout, T.A.E.*
AU  - Swegen, A.*
AU  - Skerrett-Byrne, D.A.
C1  - 73296
C2  - 56857
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Systemic changes in early pregnancy in the mare: An integrated proteomic analysis of blood plasma, histotroph, and yolk sac fluid at day 14 post-ovulation.
JO  - Proteomics Clin. Appl.
VL  - 19
IS  - 2
PB  - Wiley-v C H Verlag Gmbh
PY  - 2025
SN  - 1862-8346
ER  - 

TY  - JOUR
AB  - Scope In biomedical research, mass spectrometry imaging (MSI) can obtain spatially-resolved molecular information from tissue sections. Especially matrix-assisted laser desorption/ionization (MALDI) MSI offers, depending on the type of matrix, the detection of a broad variety of molecules ranging from metabolites to proteins, thereby facilitating the collection of multilevel molecular data. Lately, integrative clustering techniques have been developed that make use of the complementary information of multilevel molecular data in order to better stratify patient cohorts, but which have not yet been applied in the field of MSI. Materials and Methods In this study, the potential of integrative clustering is investigated for multilevel molecular MSI data to subdivide cancer patients into different prognostic groups. Metabolomic and peptidomic data are obtained by MALDI-MSI from a tissue microarray containing material of 46 esophageal cancer patients. The integrative clustering methods Similarity Network Fusion, iCluster, and moCluster are applied and compared to non-integrated clustering. Conclusion The results show that the combination of multilevel molecular data increases the capability of integrative algorithms to detect patient subgroups with different clinical outcome, compared to the single level or concatenated data. This underlines the potential of multilevel molecular data from the same subject using MSI for subsequent integrative clustering.
AU  - Balluff, B.*
AU  - Buck, A.
AU  - Martin-Lorenzo, M.*
AU  - Dewez, F.*
AU  - Langer, R.*
AU  - McDonnell, L.A.*
AU  - Walch, A.K.
AU  - Heeren, R.M.A.*
C1  - 55044
C2  - 46068
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Integrative clustering in mass spectrometry imaging for enhanced patient stratification.
JO  - Proteomics Clin. Appl.
VL  - 13
IS  - 1
PB  - Wiley-v C H Verlag Gmbh
PY  - 2019
SN  - 1862-8346
ER  - 

TY  - JOUR
AB  - Recent years have provided clear evidence for the skeletal muscle as an endocrine organ. Muscle contraction during physical activity has emerged as an important activator of the release of the proteins and peptides called myokines." Diverse proteomic profiling approaches were applied to rodent and human skeletal muscle cells to characterize the complete secretome, to study the regulation of the secretome during cell differentiation or the release of myokines upon contractile activity of myotubes. Several of the exercise-regulated factors have the potency to mediate an interorgan crosstalk. The paracrine function of the secreted peptides and proteins to regulate muscle regeneration, tissue remodeling, and trainability can have direct effects on whole-body glucose disposal and oxygen consumption. The overall composition and dynamic of the myokinome are still incompletely characterized. Recent advantages in metabolomics and lipidomics will add metabolites and lipids with autocrine, paracrine, or endocrine function to the contraction-induced secretome of the skeletal muscle. The identification of these metabolites will lead to a more comprehensive view described by a new myo(metabo)kinome consisting of peptides, proteins, and metabolites.
AU  - Weigert, C.
AU  - Lehmann, R.
AU  - Hartwig, S.*
AU  - Lerch, S.*
C1  - 31005
C2  - 34071
CY  - Weinheim
SP  - 5-18
TI  - The secretome of the working human skeletal muscle - a promising opportunity to combat the metabolic disaster?
JO  - Proteomics Clin. Appl.
VL  - 8
IS  - 1-2
PB  - Wiley-v C H Verlag Gmbh
PY  - 2014
SN  - 1862-8346
ER  - 

TY  - JOUR
AB  - PURPOSE: In this study, plasma samples from a multicentric case-control study on lymphoma were analyzed for the identification of proteins useful for diagnosis. EXPERIMENTAL DESIGN: The protein content in the plasma of 100 patients suffering from the three most common B-cell lymphomas and 100 control samples was studied with antibody microarrays composed of 810 antibodies that target cancer-associated proteins. Sample pools were screened for an identification of marker proteins. Then, the samples were analyzed individually to validate the usability of these markers. RESULTS: More than 200 proteins with disease-associated abundance changes were found. The evaluation on individual patients confirmed some molecules as robust informative markers while others were inadequate for this purpose. In addition, the analysis revealed distinct subgroups for each of the three investigated B-cell lymphoma subtypes. With this information, we delineated a classifier that discriminates the different lymphoma entities. CONCLUSIONS AND CLINICAL RELEVANCE: Variations in plasma protein abundance permit discrimination between different patient groups. After validation on a larger study cohort, the findings could have diagnostic as well as differential diagnostic potential. Beside this, methodological aspects were critically evaluated, such as the value of sample pooling for the identification of biomarkers that are useful for a diagnosis on individual patients.
AU  - Schröder, C.*
AU  - Srinivasan, H.*
AU  - Sill, M.*
AU  - Linseisen, J.
AU  - Fellenberg, K.*
AU  - Becker, N.*
AU  - Nieters, A.*
AU  - Hoheisel, J.D.*
C1  - 28641
C2  - 33513
SP  - 802-812
TI  - Plasma protein analysis of patients with different B-cell lymphomas using high-content antibody microarrays.
JO  - Proteomics Clin. Appl.
VL  - 7
IS  - 11-12
PB  - Wiley-Blackwell
PY  - 2013
SN  - 1862-8346
ER  - 

TY  - JOUR
AB  - Owing to its availability, ease of collection, and correlation with pathophysiology of diseases, urine is an attractive source for clinical proteomics. However, many proteomic studies have had only limited clinical impact, due to factors such as modest numbers of subjects, absence of disease controls, small numbers of defined biomarkers, and diversity of analytical platforms. Therefore, it is difficult to merge biomarkers from different studies into a broadly applicable human urinary proteome database. Ideally, the methodology for defining the biomarkers should combine a reasonable analysis time with high resolution, thereby enabling the profiling of adequate samples and recognition of sufficient features to yield robust diagnostic panels. CE-MS, which was used to analyze urine samples from healthy subjects and patients with various diseases, is a suitable approach for this task. The database of these datasets compiled from the urinary peptides enables the diagnosis, classification, and monitoring of a wide range of diseases. CE-MS exhibits excellent performance for biomarker discovery and allows subsequent biomarker sequencing independent of the separation platform. This approach may elucidate the pathogenesis of many diseases, and better define especially renal and urological disorders at the molecular level.
AU  - Coon, J.J.*
AU  - Zürbig, P.*
AU  - Dakna, M.*
AU  - Dominiczak, A.F.*
AU  - Decramer, S.*
AU  - Fliser, D.*
AU  - Frommberger, M.
AU  - Golovko, I.*
AU  - Good, D.M.*
AU  - Herget-Rosenthal, S.*
AU  - Jankowski, J.*
AU  - Julian, B.A.*
AU  - Kellmann, M.*
AU  - Kolch, W.*
AU  - Massy, Z.*
AU  - Novak, J.*
AU  - Rossing, K.*
AU  - Schanstra, J.P.*
AU  - Schiffer, E.*
AU  - Theodorescu, D.*
AU  - Vanholder, R.*
AU  - Weissinger, E.M.*
AU  - Mischak, H.*
AU  - Schmitt-Kopplin, P.
C1  - 2699
C2  - 25680
SP  - 964-973
TI  - CE-MS analysis of the human urinary proteome for biomarker discovery and disease diagnostics.
JO  - Proteomics Clin. Appl.
VL  - 2
IS  - 7-8
PB  - Wiley-VCH
PY  - 2008
SN  - 1862-8346
ER  - 

TY  - JOUR
AB  - We have established and validated a protocol for the peptidomic analysis of rat urine using CE coupled to MS (CE-MS). In the first experiments, the reproducibility of the CE-MS set-up and of the established preparation procedure were assessed. To establish a first rat urinary peptidome map, samples were also analyzed using CE-FT-ICR. The subsequent analysis of independent samples from two different strains (WISTAR and CD) indicated strain-specific differences, which were validated in a blinded assessment. MS/MS revealed the presence of specific fragments from well-known urinary rat peptides, such as collagens, alpha-1-antitrypsin, and serum albumin. The CE-MS-based peptidomics platform may provide novel insights into body fluids of animal models, such as rat or mice. Together with peptide identification, the technology appears to be an excellent, complimentary, and non-invasive tool to analyze toxicological or other (patho)physiological effects of pharmaceutical compounds in animal models.
AU  - Frommberger, M.
AU  - Zürbig , P.*
AU  - Jantos, J.*
AU  - Krahn, T.*
AU  - Mischak, H.*
AU  - Pich, A.*
AU  - Just, I.*
AU  - Schmitt-Kopplin, P.
AU  - Schiffer, E.*
C1  - 2683
C2  - 24557
SP  - 650-660
TI  - Peptidomic analysis of rat urine using capillary electrophoresis coupled to mass spectrometry.
JO  - Proteomics Clin. Appl.
VL  - 1
IS  - 7
PB  - Wiley-VCH
PY  - 2007
SN  - 1862-8346
ER  -