@article{KrausMathewStephenSchapranow2021,
  author    = {Kraus, Sara Milena and Mathew-Stephen, Mariet and Schapranow, Matthieu-Patrick},
  title     = {Eatomics},
  series = {Journal of proteome research},
  volume    = {20},
  journal   = {Journal of proteome research},
  number    = {1},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1535-3893},
  doi       = {10.1021/acs.jproteome.0c00398},
  pages     = {1070 -- 1078},
  year      = {2021},
  abstract  = {Quantitative proteomics data are becoming increasingly more available, and as a consequence are being analyzed and interpreted by a larger group of users. However, many of these users have less programming experience. Furthermore, experimental designs and setups are getting more complicated, especially when tissue biopsies are analyzed. Luckily, the proteomics community has already established some best practices on how to conduct quality control, differential abundance analysis and enrichment analysis. However, an easy-to-use application that wraps together all steps for the exploration and flexible analysis of quantitative proteomics data is not yet available. For Eatomics, we utilize the R Shiny framework to implement carefully chosen parts of established analysis workflows to (i) make them accessible in a user-friendly way, (ii) add a multitude of interactive exploration possibilities, and (iii) develop a unique experimental design setup module, which interactively translates a given research hypothesis into a differential abundance and enrichment analysis formula. In this, we aim to fulfill the needs of a growing group of inexperienced quantitative proteomics data analysts. Eatomics may be tested with demo data directly online via https://we.analyzegenomes.com/now/eatomics/or with the user's own data by installation from the Github repository at https://github.com/Millchmaedchen/Eatomics.},
  language  = {en}
}
@misc{PerscheidFaberKrausetal.2018,
  author    = {Perscheid, Cindy and Faber, Lukas and Kraus, Milena and Arndt, Paul and Janke, Michael and Rehfeldt, Sebastian and Schubotz, Antje and Slosarek, Tamara and Uflacker, Matthias},
  title     = {A tissue-aware gene selection approach for analyzing multi-tissue gene expression data},
  series = {2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)},
  journal   = {2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)},
  publisher = {IEEE},
  address   = {New York},
  isbn      = {978-1-5386-5488-0},
  issn      = {2156-1125},
  doi       = {10.1109/BIBM.2018.8621189},
  pages     = {2159 -- 2166},
  year      = {2018},
  abstract  = {High-throughput RNA sequencing (RNAseq) produces large data sets containing expression levels of thousands of genes. The analysis of RNAseq data leads to a better understanding of gene functions and interactions, which eventually helps to study diseases like cancer and develop effective treatments. Large-scale RNAseq expression studies on cancer comprise samples from multiple cancer types and aim to identify their distinct molecular characteristics. Analyzing samples from different cancer types implies analyzing samples from different tissue origin. Such multi-tissue RNAseq data sets require a meaningful analysis that accounts for the inherent tissue-related bias: The identified characteristics must not originate from the differences in tissue types, but from the actual differences in cancer types. However, current analysis procedures do not incorporate that aspect. As a result, we propose to integrate a tissue-awareness into the analysis of multi-tissue RNAseq data. We introduce an extension for gene selection that provides a tissue-wise context for every gene and can be flexibly combined with any existing gene selection approach. We suggest to expand conventional evaluation by additional metrics that are sensitive to the tissue-related bias. Evaluations show that especially low complexity gene selection approaches profit from introducing tissue-awareness.},
  language  = {en}
}
@article{NordmeyerKrausZiehmetal.2023,
  author    = {Nordmeyer, Sarah and Kraus, Milena and Ziehm, Matthias and Kirchner, Marieluise and Schafstedde, Marie and Kelm, Marcus and Niquet, Sylvia and Stephen, Mariet Mathew and Baczko, Istvan and Knosalla, Christoph and Schapranow, Matthieu-Patrick and Dittmar, Gunnar and Gotthardt, Michael and Falcke, Martin and Regitz-Zagrosek, Vera and Kuehne, Titus and Mertins, Philipp},
  title     = {Disease- and sex-specific differences in patients with heart valve disease},
  series = {Life Science Alliance},
  volume    = {6},
  journal   = {Life Science Alliance},
  number    = {3},
  publisher = {EMBO Press},
  address   = {Heidelberg},
  issn      = {2575-1077},
  doi       = {10.26508/lsa.202201411},
  pages     = {18},
  year      = {2023},
  abstract  = {Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease-and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies.},
  language  = {en}
}
@phdthesis{Kraus2021,
  author    = {Kraus, Sara Milena},
  title     = {A Systems Medicine approach for heart valve diseases},
  doi       = {10.25932/publishup-52226},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-522266},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xi, 186},
  year      = {2021},
  abstract  = {In Systems Medicine, in addition to high-throughput molecular data (*omics), the wealth of clinical characterization plays a major role in the overall understanding of a disease. Unique problems and challenges arise from the heterogeneity of data and require new solutions to software and analysis methods. The SMART and EurValve studies establish a Systems Medicine approach to valvular heart disease -- the primary cause of subsequent heart failure. With the aim to ascertain a holistic understanding, different *omics as well as the clinical picture of patients with aortic stenosis (AS) and mitral regurgitation (MR) are collected. Our task within the SMART consortium was to develop an IT platform for Systems Medicine as a basis for data storage, processing, and analysis as a prerequisite for collaborative research. Based on this platform, this thesis deals on the one hand with the transfer of the used Systems Biology methods to their use in the Systems Medicine context and on the other hand with the clinical and biomolecular differences of the two heart valve diseases. To advance differential expression/abundance (DE/DA) analysis software for use in Systems Medicine, we state 21 general software requirements and features of automated DE/DA software, including a novel concept for the simple formulation of experimental designs that can represent complex hypotheses, such as comparison of multiple experimental groups, and demonstrate our handling of the wealth of clinical data in two research applications DEAME and Eatomics. In user interviews, we show that novice users are empowered to formulate and test their multiple DE hypotheses based on clinical phenotype. Furthermore, we describe insights into users' general impression and expectation of the software's performance and show their intention to continue using the software for their work in the future. Both research applications cover most of the features of existing tools or even extend them, especially with respect to complex experimental designs. Eatomics is freely available to the research community as a user-friendly R Shiny application. Eatomics continued to help drive the collaborative analysis and interpretation of the proteomic profile of 75 human left myocardial tissue samples from the SMART and EurValve studies. Here, we investigate molecular changes within the two most common types of valvular heart disease: aortic valve stenosis (AS) and mitral valve regurgitation (MR). Through DE/DA analyses, we explore shared and disease-specific protein alterations, particularly signatures that could only be found in the sex-stratified analysis. In addition, we relate changes in the myocardial proteome to parameters from clinical imaging. We find comparable cardiac hypertrophy but differences in ventricular size, the extent of fibrosis, and cardiac function. We find that AS and MR show many shared remodeling effects, the most prominent of which is an increase in the extracellular matrix and a decrease in metabolism. Both effects are stronger in AS. In muscle and cytoskeletal adaptations, we see a greater increase in mechanotransduction in AS and an increase in cortical cytoskeleton in MR. The decrease in proteostasis proteins is mainly attributable to the signature of female patients with AS. We also find relevant therapeutic targets. In addition to the new findings, our work confirms several concepts from animal and heart failure studies by providing the largest collection of human tissue from in vivo collected biopsies to date. Our dataset contributing a resource for isoform-specific protein expression in two of the most common valvular heart diseases. Apart from the general proteomic landscape, we demonstrate the added value of the dataset by showing proteomic and transcriptomic evidence for increased expression of the SARS-CoV-2- receptor at pressure load but not at volume load in the left ventricle and also provide the basis of a newly developed metabolic model of the heart.},
  language  = {en}
}