@phdthesis{ZeeshangebMajeed2014,
  author    = {Zeeshan [geb. Majeed], Saman},
  title     = {Implementation of Bioinformatics Methods for miRNA and Metabolic Modelling},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102900},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Dynamic interactions and their changes are at the forefront of current research in bioinformatics and systems biology. This thesis focusses on two particular dynamic aspects of cellular adaptation: miRNA and metabolites. miRNAs have an established role in hematopoiesis and megakaryocytopoiesis, and platelet miRNAs have potential as tools for understanding basic mechanisms of platelet function. The thesis highlights the possible role of miRNAs in regulating protein translation in platelet lifespan with relevance to platelet apoptosis and identifying involved pathways and potential key regulatory molecules. Furthermore, corresponding miRNA/target mRNAs in murine platelets are identified. Moreover, key miRNAs involved in aortic aneurysm are predicted by similar techniques. The clinical relevance of miRNAs as biomarkers, targets, resulting later translational therapeutics, and tissue specific restrictors of genes expression in cardiovascular diseases is also discussed. In a second part of thesis we highlight the importance of scientific software solution development in metabolic modelling and how it can be helpful in bioinformatics tool development along with software feature analysis such as performed on metabolic flux analysis applications. We proposed the "Butterfly" approach to implement efficiently scientific software programming. Using this approach, software applications were developed for quantitative Metabolic Flux Analysis and efficient Mass Isotopomer Distribution Analysis (MIDA) in metabolic modelling as well as for data management. "LS-MIDA" allows easy and efficient MIDA analysis and, with a more powerful algorithm and database, the software "Isotopo" allows efficient analysis of metabolic flows, for instance in pathogenic bacteria (Salmonella, Listeria). All three approaches have been published (see Appendices).},
  subject      = {miRNS},
  language  = {en}
}
@article{VerghoKneitzRosenwaldetal.2014,
  author    = {Vergho, Daniel and Kneitz, Susanne and Rosenwald, Andreas and Scherer, Charlotte and Spahn, Martin and Burger, Maximilian and Riedmiller, Hubertus and Kneitz, Burkhard},
  title     = {Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma},
  doi       = {10.1186/1471-2407-14-25},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110061},
  year      = {2014},
  abstract  = {Background Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Methods Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). Results RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. Conclusions A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.},
  language  = {en}
}
@article{SchmittBackesNourkamiTutdibietal.2012,
  author    = {Schmitt, Jana and Backes, Christina and Nourkami-Tutdibi, Nasenien and Leidinger, Petra and Deutscher, Stephanie and Beier, Markus and Gessler, Manfred and Graf, Norbert and Lenhof, Hans-Peter and Keller, Andreas and Meese, Eckart},
  title     = {Treatment-independent miRNA signature in blood of wilms tumor patients},
  series = {BMC Genomics},
  volume    = {13},
  journal   = {BMC Genomics},
  number    = {379},
  doi       = {10.1186/1471-2164-13-379},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124034},
  year      = {2012},
  abstract  = {Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5\% and of patients after chemotherapy an accuracy of 97.0\%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.},
  language  = {en}
}