Browsing by Author "Nguyen, Thanh"
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Item COMPARISON OF 3D VOLUME REGISTRATION TECHNIQUES APPLIED TO NEUROSURGERY(Office of the Vice Chancellor for Research, 2012-04-13) Verma, Romil; Cottingham, Chris; Nguyen, Thanh; Kale, Ashutosh; Catania, Robin; Wright, Jacob; Christopher, Lauren; Tuceryan, Mihan; William, AlbertIntroduction: Image guided surgery requires that the pre-operative da-ta used for planning the surgery should be aligned with the patient during surgery. For this surgical application a fast, effective volume registration al-gorithm is needed. In addition, such an algorithm can also be used to devel-op surgical training presentations. This research tests existing methods of image and volume registration with synthetic 3D models and with 3D skull data. The aim of this research is to find the most promising algorithms in ac-curacy and execution time that best fit the neurosurgery application. Methods: Medical image volumes acquired from MRI or CT medical im-aging scans provided by the Indiana University School of Medicine were used as Test image cases. Additional synthetic data with ground truth was devel-oped by the Informatics students. Each test image was processed through image registration algorithms found in four common medical imaging tools: MATLAB, 3D Slicer, VolView, and VTK/ITK. The resulting registration is com-pared against the ground truth evaluated with mean squared error metrics. Algorithm execution time is measured on standard personal computer (PC) hardware. Results: Data from this extensive set of tests reveal that the current state of the art algorithms all have strengths and weaknesses. These will be categorized and presented both in a poster form and in a 3D video presenta-tion produced by Informatics students in an auto stereoscopic 3D video. Conclusions: Preliminary results show that execution of image registra-tion in real-time is a challenging task for real time neurosurgery applica-tions. Final results will be available at paper presentation. Future research will focus on optimizing registration and also implementing deformable regis-tration in real-time.Item DeCoST: A New Approach in Drug Repurposing From Control System Theory(Frontiers, 2018-06) Nguyen, Thanh; Muhammad, Syed A.; Ibrahim, Sara; Ma, Lin; Guo, Jinlei; Bai, Baogang; Zeng, Bixin; Computer and Information Science, School of ScienceIn this paper, we propose DeCoST (Drug Repurposing from Control System Theory) framework to apply control system paradigm for drug repurposing purpose. Drug repurposing has become one of the most active areas in pharmacology since the last decade. Compared to traditional drug development, drug repurposing may provide more systematic and significantly less expensive approaches in discovering new treatments for complex diseases. Although drug repurposing techniques rapidly evolve from “one: disease-gene-drug” to “multi: gene, dru” and from “lazy guilt-by-association” to “systematic model-based pattern matching,” mathematical system and control paradigm has not been widely applied to model the system biology connectivity among drugs, genes, and diseases. In this paradigm, our DeCoST framework, which is among the earliest approaches in drug repurposing with control theory paradigm, applies biological and pharmaceutical knowledge to quantify rich connective data sources among drugs, genes, and diseases to construct disease-specific mathematical model. We use linear–quadratic regulator control technique to assess the therapeutic effect of a drug in disease-specific treatment. DeCoST framework could classify between FDA-approved drugs and rejected/withdrawn drug, which is the foundation to apply DeCoST in recommending potentially new treatment. Applying DeCoST in Breast Cancer and Bladder Cancer, we reprofiled 8 promising candidate drugs for Breast Cancer ER+ (Erbitux, Flutamide, etc.), 2 drugs for Breast Cancer ER- (Daunorubicin and Donepezil) and 10 drugs for Bladder Cancer repurposing (Zafirlukast, Tenofovir, etc.).Item Developing New Image Registration Techniques and 3D Displays for Neuroimaging and Neurosurgery(Office of the Vice Chancellor for Research, 2013-04-05) Zheng, Yuese; Jing, Yici; Nguyen, Thanh; Zajac, Sarah; Wright, Jacob; Catania, RobinImage guided surgery requires that the pre-operative data used for planning the surgery should be aligned with the patient during surgery. For this surgical application a fast, effective volume registration algorithm is needed. In addition, such an algorithm can also be used to develop surgical training presentations. This research extends existing methods and techniques to improve convergence and speed of execution. The aim is to find the most promising speed improvements while maintaining accuracy to best fit the neurosurgery application. In the recent phase, we focus on feature extraction and the time-accuracy trade-off. Medical image volumes acquired from MRI or CT medical imaging scans provided by the Indiana University School of Medicine were used as test image cases. Additional synthetic data with ground truth is developed by the Informatics students. The speed-enhancements to the registration are compared against the ground truth evaluated with mean squared error metrics. Algorithm execution time with and without speed improvement is measured on standard personal computer (PC) hardware. Additionally, the informatics students are developing a 3D movie that shows the surgical and preoperative data overlay, which presents the results of the speed improvements from the remaining students’ work. Our testing indicates that an intelligent subset of the data points that are needed for registration should improve the speed significantly. Preliminary results show that even though image registration in real-time is a challenging task for real time neurosurgery applications, intelligent preprocessing provides a promising solution. Final results will be available at paper presentation.Item DMAP: a connectivity map database to enable identification of novel drug repositioning candidates(BioMed Central, 2015-09-25) Huang, Hui; Nguyen, Thanh; Ibrahim, Sara; Shantharam, Sandeep; Yue, Zongliang; Chen, Jake Yue; Department of Computer & Information Science, School of ScienceBACKGROUND: Drug repositioning is a cost-efficient and time-saving process to drug development compared to traditional techniques. A systematic method to drug repositioning is to identify candidate drug's gene expression profiles on target disease models and determine how similar these profiles are to approved drugs. Databases such as the CMAP have been developed recently to help with systematic drug repositioning. METHODS: To overcome the limitation of connectivity maps on data coverage, we constructed a comprehensive in silico drug-protein connectivity map called DMAP, which contains directed drug-to-protein effects and effect scores. The drug-to-protein effect scores are compiled from all database entries between the drug and protein have been previously observed and provide a confidence measure on the quality of such drug-to-protein effects. RESULTS: In DMAP, we have compiled the direct effects between 24,121 PubChem Compound ID (CID), which were mapped from 289,571 chemical entities recognized from public literature, and 5,196 reviewed Uniprot proteins. DMAP compiles a total of 438,004 chemical-to-protein effect relationships. Compared to CMAP, DMAP shows an increase of 221 folds in the number of chemicals and 1.92 fold in the number of ATC codes. Furthermore, by overlapping DMAP chemicals with the approved drugs with known indications from the TTD database and literature, we obtained 982 drugs and 622 diseases; meanwhile, we only obtained 394 drugs with known indication from CMAP. To validate the feasibility of applying new DMAP for systematic drug repositioning, we compared the performance of DMAP and the well-known CMAP database on two popular computational techniques: drug-drug-similarity-based method with leave-one-out validation and Kolmogorov-Smirnov scoring based method. In drug-drug-similarity-based method, the drug repositioning prediction using DMAP achieved an Area-Under-Curve (AUC) score of 0.82, compared with that using CMAP, AUC = 0.64. For Kolmogorov-Smirnov scoring based method, with DMAP, we were able to retrieve several drug indications which could not be retrieved using CMAP. DMAP data can be queried using the existing C2MAP server or downloaded freely at: http://bio.informatics.iupui.edu/cmaps CONCLUSIONS: Reliable measurements of how drug affect disease-related proteins are critical to ongoing drug development in the genome medicine era. We demonstrated that DMAP can help drug development professionals assess drug-to-protein relationship data and improve chances of success for systematic drug repositioning efforts.Item Identification and Optimal Control of Large-Scale Systems Using Selective Decentralization(IEEE, 2016-10) Nguyen, Thanh; Mukhopadhyay, Snehasis; Computer and Information Science, School of ScienceIn this paper, we explore the capability of selective decentralization in improving the control performance for unknown large-scale systems using model-based approaches. In selective decentralization, we explore all of the possible communication policies among subsystems and show that with the appropriate switching among the resulting multiple identification models (with corresponding communication policies), such selective decentralization significantly outperforms a centralized identification model when the system is weakly interconnected, and performs at least equivalent to the centralized model when the system is strongly interconnected. To derive the sub-optimal control, our control design include two phases. First, we apply system identification to train the approximation model for the unknown system. Second, we find the suboptimal solution of the Halminton-Jacobi-Bellman (HJB) equation to derive the suboptimal control. In linear systems, the HJB equation transforms to the well-solved Riccati equation with closed-form solution. In nonlinear systems, we discretize the approximation model in order to acquire the control unit by using dynamic programming methods for the resulting Markov Decision Process (MDP). We compare the performance among the selective decentralization, the complete decentralization and the centralization in our two-phase control design. Our results show that selective decentralization outperforms the complete decentralization and the centralization approaches when the systems are completely decoupled or strongly interconnected.Item Multidisciplinary Optimization in Decentralized Reinforcement Learning(IEEE, 2017-12) Nguyen, Thanh; Mukhopadhyay, Snehasis; Computer and Information Science, School of ScienceMultidisciplinary Optimization (MDO) is one of the most popular techniques in aerospace engineering, where the system is complex and includes the knowledge from multiple fields. However, according to the best of our knowledge, MDO has not been widely applied in decentralized reinforcement learning (RL) due to the `unknown' nature of the RL problems. In this work, we apply the MDO in decentralized RL. In our MDO design, each learning agent uses system identification to closely approximate the environment and tackle the `unknown' nature of the RL. Then, the agents apply the MDO principles to compute the control solution using Monte Carlo and Markov Decision Process techniques. We examined two options of MDO designs: the multidisciplinary feasible and the individual discipline feasible options, which are suitable for multi-agent learning. Our results show that the MDO individual discipline feasible option could successfully learn how to control the system. The MDO approach shows better performance than the completely decentralization and centralization approaches.Item PAGER: constructing PAGs and new PAG-PAG relationships for network biology(Oxford University Press, 2015-06-15) Yue, Zongliang; Kshirsagar, Madhura M.; Nguyen, Thanh; Suphavilai, Chayaporn; Neylon, Michael T.; Zhu, Liugen; Ratliff, Timothy; Chen, Jake Yue; Department of Computer & Information Science, School of ScienceIn this article, we described a new database framework to perform integrative "gene-set, network, and pathway analysis" (GNPA). In this framework, we integrated heterogeneous data on pathways, annotated list, and gene-sets (PAGs) into a PAG electronic repository (PAGER). PAGs in the PAGER database are organized into P-type, A-type and G-type PAGs with a three-letter-code standard naming convention. The PAGER database currently compiles 44 313 genes from 5 species including human, 38 663 PAGs, 324 830 gene-gene relationships and two types of 3 174 323 PAG-PAG regulatory relationships-co-membership based and regulatory relationship based. To help users assess each PAG's biological relevance, we developed a cohesion measure called Cohesion Coefficient (CoCo), which is capable of disambiguating between biologically significant PAGs and random PAGs with an area-under-curve performance of 0.98. PAGER database was set up to help users to search and retrieve PAGs from its online web interface. PAGER enable advanced users to build PAG-PAG regulatory networks that provide complementary biological insights not found in gene set analysis or individual gene network analysis. We provide a case study using cancer functional genomics data sets to demonstrate how integrative GNPA help improve network biology data coverage and therefore biological interpretability. The PAGER database can be accessible openly at http://discovery.informatics.iupui.edu/PAGER/.Item Selective decentralization to improve reinforcement learning in unknown linear noisy systems(IEEE, 2017-11) Nguyen, Thanh; Mukhopadhyay, Snehasis; Computer and Information Science, School of ScienceIn this paper, we answer the question of to what extend selective decentralization could enhance the learning and control performance when the system is noisy and unknown. Compared to the previous works in selective decentralization, in this paper, we add the system noise as another complexity in the learning and control problem. Thus, we only perform analysis for some simple toy examples of noisy linear system. In linear system, the Halminton-Jaccobi-Bellman (HJB) equation becomes Riccati equation with closed-form solution. Our previous framework in learning and control unknown system is based on the following principle: approximating the system using identification in order to apply model-based solution. Therefore, this paper would explore the learning and control performance on two aspects: system identification error and system stabilization. Our results show that selective decentralization show better learning performance than the centralization when the noise level is low.Item Selectively Decentralized Q-Learning(IEEE, 2017-10) Nguyen, Thanh; Mukhopadhyay, Snehasis; Computer and Information Science, School of ScienceIn this paper, we explore the capability of selectively decentralized Q-learning approach in learning how to optimally stabilize control systems, as compared to the centralized approach. We focus on problems in which the systems are completely unknown except the possible domain knowledge that allow us to decentralize into subsystems. In selective decentralization, we explore all of the possible communication policies among subsystems and use the cumulative gained Q-value as the metric to decide which decentralization scheme should be used for controlling. The results show that the selectively decentralized approach not only stabilizes the system faster but also shows superior converging speed on gained Q-value in different systems with different interconnection strength. In addition, the selectively decentralized converging time does not seem to grow exponentially with the system dimensionality. Practically, this fact implies that the selectively decentralized Q-learning could be used as an alternative approach in large-scale unknown control system, where in theory, the Hamilton-Jacobi-Bellman-equation approach is difficult to derive the close-form solution.Item "Super Gene Set" Causal Relationship Discovery from Functional Genomics Data(IEEE, 2018-11) Yue, Zongliang; Neylon, Michael T.; Nguyen, Thanh; Ratliff, Timothy; Chen, Jake Yue; BioHealth Informatics, School of Informatics and ComputingIn this article, we present a computational framework to identify "causal relationships" among super gene sets. For "causal relationships," we refer to both stimulatory and inhibitory regulatory relationships, regardless of through direct or indirect mechanisms. For super gene sets, we refer to "pathways, annotated lists, and gene signatures," or PAGs. To identify causal relationships among PAGs, we extend the previous work on identifying PAG-to-PAG regulatory relationships by further requiring them to be significantly enriched with gene-to-gene co-expression pairs across the two PAGs involved. This is achieved by developing a quantitative metric based on PAG-to-PAG Co-expressions (PPC), which we use to infer the likelihood that PAG-to-PAG relationships under examination are causal-either stimulatory or inhibitory. Since true causal relationships are unknown, we approximate the overall performance of inferring causal relationships with the performance of recalling known r-type PAG-to-PAG relationships from causal PAG-to-PAG inference, using a functional genomics benchmark dataset from the GEO database. We report the area-under-curve (AUC) performance for both precision and recall being 0.81. By applying our framework to a myeloid-derived suppressor cells (MDSC) dataset, we further demonstrate that this framework is effective in helping build multi-scale biomolecular systems models with new insights on regulatory and causal links for downstream biological interpretations.