@phdthesis{Perscheid2023,
  author    = {Perscheid, Cindy},
  title     = {Integrative biomarker detection using prior knowledge on gene expression data sets},
  doi       = {10.25932/publishup-58241},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-582418},
  school      = {Universit{\"a}t Potsdam},
  pages     = {ix, 197},
  year      = {2023},
  abstract  = {Gene expression data is analyzed to identify biomarkers, e.g. relevant genes, which serve for diagnostic, predictive, or prognostic use. Traditional approaches for biomarker detection select distinctive features from the data based exclusively on the signals therein, facing multiple shortcomings in regards to overfitting, biomarker robustness, and actual biological relevance. Prior knowledge approaches are expected to address these issues by incorporating prior biological knowledge, e.g. on gene-disease associations, into the actual analysis. However, prior knowledge approaches are currently not widely applied in practice because they are often use-case specific and seldom applicable in a different scope. This leads to a lack of comparability of prior knowledge approaches, which in turn makes it currently impossible to assess their effectiveness in a broader context. Our work addresses the aforementioned issues with three contributions. Our first contribution provides formal definitions for both prior knowledge and the flexible integration thereof into the feature selection process. Central to these concepts is the automatic retrieval of prior knowledge from online knowledge bases, which allows for streamlining the retrieval process and agreeing on a uniform definition for prior knowledge. We subsequently describe novel and generalized prior knowledge approaches that are flexible regarding the used prior knowledge and applicable to varying use case domains. Our second contribution is the benchmarking platform Comprior. Comprior applies the aforementioned concepts in practice and allows for flexibly setting up comprehensive benchmarking studies for examining the performance of existing and novel prior knowledge approaches. It streamlines the retrieval of prior knowledge and allows for combining it with prior knowledge approaches. Comprior demonstrates the practical applicability of our concepts and further fosters the overall development and comparability of prior knowledge approaches. Our third contribution is a comprehensive case study on the effectiveness of prior knowledge approaches. For that, we used Comprior and tested a broad range of both traditional and prior knowledge approaches in combination with multiple knowledge bases on data sets from multiple disease domains. Ultimately, our case study constitutes a thorough assessment of a) the suitability of selected knowledge bases for integration, b) the impact of prior knowledge being applied at different integration levels, and c) the improvements in terms of classification performance, biological relevance, and overall robustness. In summary, our contributions demonstrate that generalized concepts for prior knowledge and a streamlined retrieval process improve the applicability of prior knowledge approaches. Results from our case study show that the integration of prior knowledge positively affects biomarker results, particularly regarding their robustness. Our findings provide the first in-depth insights on the effectiveness of prior knowledge approaches and build a valuable foundation for future research.},
  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{PerscheidGrasnickUflacker2019,
  author    = {Perscheid, Cindy and Grasnick, Bastien and Uflacker, Matthias},
  title     = {Integrative Gene Selection on Gene Expression Data},
  series = {Journal of Integrative Bioinformatics},
  volume    = {16},
  journal   = {Journal of Integrative Bioinformatics},
  number    = {1},
  publisher = {De Gruyter},
  address   = {Berlin},
  issn      = {1613-4516},
  doi       = {10.1515/jib-2018-0064},
  pages     = {17},
  year      = {2019},
  abstract  = {The advance of high-throughput RNA-Sequencing techniques enables researchers to analyze the complete gene activity in particular cells. From the insights of such analyses, researchers can identify disease-specific expression profiles, thus understand complex diseases like cancer, and eventually develop effective measures for diagnosis and treatment. The high dimensionality of gene expression data poses challenges to its computational analysis, which is addressed with measures of gene selection. Traditional gene selection approaches base their findings on statistical analyses of the actual expression levels, which implies several drawbacks when it comes to accurately identifying the underlying biological processes. In turn, integrative approaches include curated information on biological processes from external knowledge bases during gene selection, which promises to lead to better interpretability and improved predictive performance. Our work compares the performance of traditional and integrative gene selection approaches. Moreover, we propose a straightforward approach to integrate external knowledge with traditional gene selection approaches. We introduce a framework enabling the automatic external knowledge integration, gene selection, and evaluation. Evaluation results prove our framework to be a useful tool for evaluation and show that integration of external knowledge improves overall analysis results.},
  language  = {en}
}
@article{Perscheid2021,
  author    = {Perscheid, Cindy},
  title     = {Comprior},
  series = {BMC Bioinformatics},
  volume    = {22},
  journal   = {BMC Bioinformatics},
  publisher = {Springer Nature},
  address   = {London},
  issn      = {1471-2105},
  doi       = {10.1186/s12859-021-04308-z},
  pages     = {1 -- 15},
  year      = {2021},
  abstract  = {Background Reproducible benchmarking is important for assessing the effectiveness of novel feature selection approaches applied on gene expression data, especially for prior knowledge approaches that incorporate biological information from online knowledge bases. However, no full-fledged benchmarking system exists that is extensible, provides built-in feature selection approaches, and a comprehensive result assessment encompassing classification performance, robustness, and biological relevance. Moreover, the particular needs of prior knowledge feature selection approaches, i.e. uniform access to knowledge bases, are not addressed. As a consequence, prior knowledge approaches are not evaluated amongst each other, leaving open questions regarding their effectiveness. Results We present the Comprior benchmark tool, which facilitates the rapid development and effortless benchmarking of feature selection approaches, with a special focus on prior knowledge approaches. Comprior is extensible by custom approaches, offers built-in standard feature selection approaches, enables uniform access to multiple knowledge bases, and provides a customizable evaluation infrastructure to compare multiple feature selection approaches regarding their classification performance, robustness, runtime, and biological relevance. Conclusion Comprior allows reproducible benchmarking especially of prior knowledge approaches, which facilitates their applicability and for the first time enables a comprehensive assessment of their effectiveness},
  language  = {en}
}
@misc{Perscheid2021,
  author    = {Perscheid, Cindy},
  title     = {Comprior: facilitating the implementation and automated benchmarking of prior knowledge-based feature selection approaches on gene expression data sets},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  doi       = {10.25932/publishup-54894},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-548943},
  pages     = {1 -- 15},
  year      = {2021},
  abstract  = {Background Reproducible benchmarking is important for assessing the effectiveness of novel feature selection approaches applied on gene expression data, especially for prior knowledge approaches that incorporate biological information from online knowledge bases. However, no full-fledged benchmarking system exists that is extensible, provides built-in feature selection approaches, and a comprehensive result assessment encompassing classification performance, robustness, and biological relevance. Moreover, the particular needs of prior knowledge feature selection approaches, i.e. uniform access to knowledge bases, are not addressed. As a consequence, prior knowledge approaches are not evaluated amongst each other, leaving open questions regarding their effectiveness. Results We present the Comprior benchmark tool, which facilitates the rapid development and effortless benchmarking of feature selection approaches, with a special focus on prior knowledge approaches. Comprior is extensible by custom approaches, offers built-in standard feature selection approaches, enables uniform access to multiple knowledge bases, and provides a customizable evaluation infrastructure to compare multiple feature selection approaches regarding their classification performance, robustness, runtime, and biological relevance. Conclusion Comprior allows reproducible benchmarking especially of prior knowledge approaches, which facilitates their applicability and for the first time enables a comprehensive assessment of their effectiveness},
  language  = {en}
}