My group continued to work on computational methods to study the dynamics of biological networks, impact of genetic variations and structural variation on gene expression, organismal phenotype in the context of complex diseases, analysis of new high throughput experimental data, and developing methods for analysis of HT-SELEX data. We are developing a comprehensive software package, AptaTools, for analysis of HT-SELEX data.
Aimi ng at providing a comprehensive HT-SELEX data-analysis software. AptaTools is designed with computational speed in mind and capable of simultaneously processing many selection cycles due to its parallel processing capabilities. It is hence suitable for cloud computing and deployment. Finally, a graphical user interface, AptaGUI, allows for efficient and dynamic visualization of the analysis. We expect, that this toolbox will become an indispensable tool for guiding the selection of aptamers as well as for uncovering further general properties of the selection process and ultimately lead to a better utilization of HT-SELEX results. As part of this package, we have developed new clustering algorithm, AptaCluster which is, up to our best knowledge, the only currently available tool capable of efficiently clustering entire aptamer pools of more than 20 Million sequences. The paper describing this algorithm has been accepted for oral presentation at RECOMB 2014 - a pioneer conference in Computational Biology (1). We also continued to work on methods to delineate genetic underpinnings of complex traits. Following the development of our two new methods, Module Cover, and the probabilistic cancer model reported last year, we are working on combining the two methods and applying the combined approach to study TCGA PanCancer data. We also continued the collaboration with Brian Oliver's group on gene regulation and on modeling of the impact of gene copy number of fly phenotype. In this study we use DrosDel fly panel. Flies in this panels have deletions of various chromosomal regions making some of the genes to have a single copy. This main work is still under progress. We contributed to the related paper (2). Continuing a successful collaboration with David Levens we continue our work on the impact of transcription induced supercoiling on gene regulation and formation of non-B-DNA structures (3). A paper reporting the results of this study in the context of non-B-DNA structures is under preparation. Focusing on more computational analysis, we leveraged 1000 human genome project analyzed the impact of nucleotide variations. The paper describing these results is under revision. Finally, we continue to support other groups by providing computational expertise for their studies (4-6).

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Budget End
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7
Fiscal Year
2014
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Indirect Cost
Name
National Library of Medicine
Department
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Wang, Yijie; Hoinka, Jan; Liang, Yong et al. (2018) AptaBlocks: Designing RNA complexes and accelerating RNA-based drug delivery systems. Nucleic Acids Res 46:8133-8142
Shubham, Shambhavi; Hoinka, Jan; Banerjee, Soma et al. (2018) A 2'FY-RNA Motif Defines an Aptamer for Ebolavirus Secreted Protein. Sci Rep 8:12373
Guo, Jing; Chen, Hao; Yang, Peng et al. (2018) LDSplitDB: a database for studies of meiotic recombination hotspots in MHC using human genomic data. BMC Med Genomics 11:27
Fröhlich, Holger; Balling, Rudi; Beerenwinkel, Niko et al. (2018) From hype to reality: data science enabling personalized medicine. BMC Med 16:150
Hoinka, Jan; Backofen, Rolf; Przytycka, Teresa M (2018) AptaSUITE: A Full-Featured Bioinformatics Framework for the Comprehensive Analysis of Aptamers from HT-SELEX Experiments. Mol Ther Nucleic Acids 11:515-517
Huang, Xiaoqing; Wojtowicz, Damian; Przytycka, Teresa M (2017) Detecting presence of mutational signatures in cancer with confidence. Bioinformatics :
Kouzine, Fedor; Wojtowicz, Damian; Baranello, Laura et al. (2017) Permanganate/S1 Nuclease Footprinting Reveals Non-B DNA Structures with Regulatory Potential across a Mammalian Genome. Cell Syst 4:344-356.e7
Hacker, David E; Hoinka, Jan; Iqbal, Emil S et al. (2017) Highly Constrained Bicyclic Scaffolds for the Discovery of Protease-Stable Peptides via mRNA Display. ACS Chem Biol 12:795-804
Dao, Phuong; Kim, Yoo-Ah; Wojtowicz, Damian et al. (2017) BeWith: A Between-Within method to discover relationships between cancer modules via integrated analysis of mutual exclusivity, co-occurrence and functional interactions. PLoS Comput Biol 13:e1005695
Lee, Hangnoh; Cho, Dong-Yeon; Wojtowicz, Damian et al. (2017) Dosage-Dependent Expression Variation Suppressed on the Drosophila Male X Chromosome. G3 (Bethesda) :

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