QuanAnts Machine: A Quantum Algorithm for Biomarker Discovery

The discovery of biomarker sets for a targeted pathway is a challenging problem in biomedical medicine, which is computationally prohibited on classical algorithms due to the massive search space. Here, I present a quantum algorithm named QuantAnts Machine to address the task. The proposed algorithm is a quantum analog of the classical Ant Colony Optimization (ACO). We create the mixture of multi-domain from genetic networks by representation theory, enabling the search of biomarkers from the multi-modality of the human genome. Although the proposed model can be generalized, we investigate the RAS-mutational activation in this work. To the end, QuantAnts Machine discovers rarely-known biomarkers in clinical-associated domain for RAS-activation pathway, including COL5A1, COL5A2, CCT5, MTSS1 and NCAPD2. Besides, the model also suggests several therapeutic-targets such as JUP, CD9, CD34 and CD74

Investigations into the mechanisms of telomere structure and function

2012 Spring.Includes bibliographical references.Telomere dysfunction is most commonly defined as critical shortening; i.e., loss of telomere sequence due to a variety of causes, usually the end-replication problem. However telomeres and their arsenal of associated proteins also provide essential end-capping structure that protects the ends of linear eukaryotic chromosomes. The overall goal of the studies presented here was to provide new insight into underlying mechanisms of telomeric structure and function. We examined the role of telomere function in Acute Myeloid Leukemia. We observed genomic instability in association with radiation-induced AML, and this association was observed following AML induction with both gamma (γ)- ray and 1 Gev 56Fe ion exposure. Furthermore, we observed a clonal fusion event involving telomeres in a human AML cell line. Taken together, our AML studies underline the importance of genome stability and its link to carcinogenesis. We previously reported a role for the DNA damage repair protein DNA-PKcs in mammalian telomere end-capping function, where inappropriate telomere fusions, as well as telomere fusions to other broken DNA ends, were observed in DNA-PKcs deficient backgrounds. DNA-PKcs has many proposed phosphorylation substrates, one of the most intriguing and relevant being the recently identified heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), an RNA binding protein that associates with telomeres. It is also now well accepted that telomeres are transcribed into telomeric repeat-containing RNAs, or TERRA, which are thought to contribute to telomeric chromatin structure. Taken together, we hypothesized that DNA-PKcs mediated phosphorylation of hnRNA1 plays an important role in tethering TERRA to telomere ends, thereby possibly contributing to telomere chromatin structure and function. Our data suggests that TERRA localization at telomeres is independent of hnRNP A1 and DNA-PKcs kinase activity. Rather, we observed decreased TERRA levels following DNA-PKcs kinase inhibition, suggesting DNA-PKcs indirectly regulates TERRA levels. Depletion of hnRNP A1 did not influence TERRA levels, but resulted in elevated frequencies of what have previously been termed "fragile" telomeres and telomere sister chromatid exchange (T-SCE), both indicative of a role for hnRNP A1 in facilitating telomere replication

Ultra-large alignments using Phylogeny-aware Profiles

Many biological questions, including the estimation of deep evolutionary histories and the detection of remote homology between protein sequences, rely upon multiple sequence alignments (MSAs) and phylogenetic trees of large datasets. However, accurate large-scale multiple sequence alignment is very difficult, especially when the dataset contains fragmentary sequences. We present UPP, an MSA method that uses a new machine learning technique - the Ensemble of Hidden Markov Models - that we propose here. UPP produces highly accurate alignments for both nucleotide and amino acid sequences, even on ultra-large datasets or datasets containing fragmentary sequences. UPP is available at https://github.com/smirarab/sepp.Comment: Online supplemental materials and data are available at http://www.cs.utexas.edu/users/phylo/software/upp

Molecular characterization of the interaction between peripherin-2 and opsins in rod and cone photoreceptors

The tetraspanin peripherin-2 is a glyco-membrane protein exclusively expressed in the outer segments of rod and cone photoreceptors. Mutations in peripherin-2 are associated with retinal disorders characterized by Degeneration of rod or cone cells. Previous unpublished work identified peripherin-2 as a potential novel part of the protein complex comprising the B-subunit of the cyclic nucleotide-gated channel (CNGB1a and the light detector rhodopsin. In the first part of this study, using a combination of protein biochemical and FRET approaches in transfected HEK293 cells and in virally transduced murine rod outer segments, it could be demonstrated that peripherin-2 simultaneously binds to both, CNGB1a and rhodopsin. The interaction between peripherin-2 and rhodopsin was not described in previous studies. The binding domain mediating the peripherin-2/rhodopsin interaction could be narrowed down to the fourth transmembrane domain (TM4) of peripherin-2. Finally, the data revealed that the G266D point mutation in TM4 of peripherin-2 that is linked to a rod degenerative disease selectively disrupts the peripherin-2/rhodopsin interaction. To analyze if peripherin-2 also binds to cone opsins in the second part of this study, a similar experimental approach was conducted as used for the investigation of the peripherin-2/rhodopsin interaction. In this context, it was unveiled that peripherin-2 binds to both, short wavelength-and medium wavelength-sensitive cone opsin (S-opsin and M-opsin, respectively) in transfected HEK293 cells and in outer segments of transduced murine cones. Co-immunoprecipitation and quantitative FRET analysis revealed that binding of peripherin-2 to M-opsin was stronger than the peripherin-2/S-opsin interaction. This result was supported by transmission electron microscopy studies using gold particles coupled to opsin- and peripherin-2-specific antibodies. Finally, quantitative FRET analysis in transfected HEK293 cells and in transduced cone outer segments demonstrated that the V268I Point mutation in TM4 of peripherin-2 associated with a degenerative cone disease significantly attenuates the peripherin-2/M-opsin interaction. Taken together, this study provides a proof-of-principle for FRET-based analysis of protein-protein interactions in the outer segments of rod and cone photoreceptors. This approach led to the identification of hitherto unknown Protein complexes between peripherin-2 and opsins suggesting a novel physiological role of peripherin-2 in rods and cones. Finally, Analysis of disease-linked point mutations unveiled the molecular determinants of the peripherin-2/opsin interaction. These results might contribute to understanding the differential penetrance of certain point mutations in rods and cones

Langmuir-Maxwell and Langmuir-Smoluchowski boundary conditions for thermal gas flow simulations in hypersonic aerodynamics

The simulation of nonequilibrium thermal gas flow is important for the aerothermodynamic design of re-entry and other high-altitude vehicles. In computational fluid dynamics, the accuracy of the solution to the Navier–Stokes–Fourier (N–S–F) equations depends on the accuracy of the surface boundary conditions. We propose new boundary conditions (called the Langmuir–Maxwell and the Langmuir–Smoluchowski conditions), for use with the N–S–F equations, which combine the Langmuir surface adsorption isotherm with the Maxwell/Smoluchowski slip/jump conditions in order to capture some of the physical processes involved in gas flow over a surface. These new conditions are validated for flat plate flow, circular cylinder in cross-flow, and the flow over a sharp wedge for Mach numbers ranging from 6 to 24, and for argon and nitrogen as the working gases. Our simulation results show that the new boundary conditions give better predictions for the surface pressures, compared with published experimental and DSMC data

Using Dynamic Active Subspaces to Construct Surrogate Models for Calibrating Tumor Growth Models to Data

While the use of complex ODE models describing tumor growth and tumor-immune interactions may be desirable for accurately representing the biological mechanisms that govern tumor growth, the high-dimensionality of the parameter space can make it difficult to uniquely identify optimal parameter estimates during model calibration. Construction of a surrogate model that can accurately approximate the quantity of interest with fewer parameters may enable us to fit this alternate model to the data in place of the original ODE system. In this investigation, we consider how active subspaces may be used to construct time-dependent surrogate models with reduced parameter dimension, and analyze the trade-offs in parameter identifiability, model fit error, and computational run-time to provide a roadmap for ensuring an identifiable parameter set during model calibration

Linking Relationship Marketing to Customer Loyalty in The E-Banking Context: The Central Role of Customer Satisfaction

This research examines the interrelationships between relationship marketing, customer satisfaction and customer loyalty in e-banking’s context. The study was conducted in two phases: In-depth interviews and a quantitative survey with a sample of 690 Vietnamese individual and corporate e-banking customers. The research results show that customer satisfaction mediates the impact of relationship marketing on customer loyalty among individual customers. Meanwhile, instead of customer satisfaction, relationship marketing significantly and directly contributes to the loyalty of the corporate customer group. The significance and magnitude of the effects that the five dimensions of relationship marketing’s effectiveness have on customer satisfaction and loyalty, which include the banks’ commitment, customer experience, process-driven approach, service reliability and application of technology, are also different between the two customer segments. This study theoretically contributes to the research stream regarding the mechanism underlying the relationship between relationship marketing’s effectiveness and customer loyalty in the e-banking context, and proposes practical implications for commercial banks to effectively apply relationship marketing in the virtual business environment

Robust model predictive kinematic tracking control with terminal region for wheeled robotic systems

This paper addresses the nonlinear model predictive control (MPC) for wheeled mobile robots (WMRs) under external disturbance. The decoupling technique is utilized based on the non-holonomic constraint description for separating the WMR model. This method is able to achieve the under-actuated kinematic sub-system without disturbance and fully-actuated dynamic sub-system in presence of disturbance. Thanks to the decoupling technique, the disturbance is lumped into dynamic sub-system. The novelty lies in that the MPC-based tracking control with fixed initial point guarantees the stability based on a new establishment of terminal region and equivalent terminal controller. The feasibility problem is demonstrated to lead the tracking problem using theoretical analysis. Moreover, the control structure is inserted more the robust nonlinear dynamic controller. The effectiveness and advantages of the proposed control scheme are verified by numerical simulations using Yamip tool

ViFi: accurate detection of viral integration and mRNA fusion reveals indiscriminate and unregulated transcription in proximal genomic regions in cervical cancer.

The integration of viral sequences into the host genome is an important driver of tumorigenesis in many viral mediated cancers, notably cervical cancer and hepatocellular carcinoma. We present ViFi, a computational method that combines phylogenetic methods with reference-based read mapping to detect viral integrations. In contrast with read-based reference mapping approaches, ViFi is faster, and shows high precision and sensitivity on both simulated and biological data, even when the integrated virus is a novel strain or highly mutated. We applied ViFi to matched genomic and mRNA data from 68 cervical cancer samples from TCGA and found high concordance between the two. Surprisingly, viral integration resulted in a dramatic transcriptional upregulation in all proximal elements, including LINEs and LTRs that are not normally transcribed. This upregulation is highly correlated with the presence of a viral gene fused with a downstream human element. Moreover, genomic rearrangements suggest the formation of apparent circular extrachromosomal (ecDNA) human-viral structures. Our results suggest the presence of apparent small circular fusion viral/human ecDNA, which correlates with indiscriminate and unregulated expression of proximal genomic elements, potentially contributing to the pathogenesis of HPV-associated cervical cancers. ViFi is available at https://github.com/namphuon/ViFi

Secrecy performance of TAS/SC-based multi-hop harvest-to-transmit cognitive WSNs under joint constraint of interference and hardware imperfection

In this paper, we evaluate the secrecy performance of multi-hop cognitive wireless sensor networks (WSNs). In the secondary network, a source transmits its data to a destination via the multi-hop relaying model using the transmit antenna selection (TAS)/selection combining (SC) technique at each hop, in the presence of an eavesdropper who wants to receive the data illegally. The secondary transmitters, including the source and intermediate relays, have to harvest energy from radio-frequency signals of a power beacon for transmitting the source data. Moreover, their transmit power must be adjusted to satisfy the quality of service (QoS) of the primary network. Under the joint impact of hardware imperfection and interference constraint, expressions for the transmit power for the secondary transmitters are derived. We also derive exact and asymptotic expressions of secrecy outage probability (SOP) and probability of non-zero secrecy capacity (PNSC) for the proposed protocol over Rayleigh fading channel. The derivations are then verified by Monte Carlo simulations.Web of Science195art. no. 116