Data integration, pathway analysis and mining for systems biology

Post-genomic molecular biology embodies high-throughput experimental techniques and hence is a data-rich field. The goal of this thesis is to develop bioinformatics methods to utilise publicly available data in order to produce knowledge and to aid mining of newly generated data. As an example of knowledge or hypothesis generation, consider function prediction of biological molecules. Assignment of protein function is a non-trivial task owing to the fact that the same protein may be involved in different biological processes, depending on the state of the biological system and protein localisation. The function of a gene or a gene product may be provided as a textual description in a gene or protein annotation database. Such textual descriptions lack in providing the contextual meaning of the gene function. Therefore, we need ways to represent the meaning in a formal way. Here we apply data integration approach to provide rich representation that enables context-sensitive mining of biological data in terms of integrated networks and conceptual spaces. Context-sensitive gene function annotation follows naturally from this framework, as a particular application. Next, knowledge that is already publicly available can be used to aid mining of new experimental data. We developed an integrative bioinformatics method that utilises publicly available knowledge of protein-protein interactions, metabolic networks and transcriptional regulatory networks to analyse transcriptomics data and predict altered biological processes. We applied this method to a study of dynamic response of Saccharomyces cerevisiae to oxidative stress. The application of our method revealed dynamically altered biological functions in response to oxidative stress, which were validated by comprehensive in vivo metabolomics experiments. The results provided in this thesis indicate that integration of heterogeneous biological data facilitates advanced mining of the data. The methods can be applied for gaining insight into functions of genes, gene products and other molecules, as well as for offering functional interpretation to transcriptomics and metabolomics experiments

Enantioselective synthesis using crude enzymes

Chiral trans-2-aryloxycyclohexan-l-ols, trans-2-alkoxy cyclohexan-1-ols, trans-2-arylcyclohexan-l-ols, homoallyl alcohols, 1-aryl-1-alkanols, 1,2-diphenylethane-l,2-diol are prepared in high optical purities via enantioselective hydrolysis of acetates of the corresponding racemic alcohols using crude enzymes such as pig liver acetone powder (PLAP), goat liver acetone powder (GLAP), chicken liver acetone powder (CLAP) and bovine liver acetone powder (BLAP)

Biosynthesis, Characterization and Antibacterial activity of Silver nanoparticles of Excoecaria agallocha L. fruit extract

In this present study, Excoecaria agallocha fruit aqueous extract was used to synthesize Silver Nano Particles (Ag NPs/SNPs) which has proven as eco-friendly, nontoxic, less time consuming and energy saving. The synthesized SNPs were characterized by UV-Visible spectroscopy, FTIR and SEM studies. The SNPs were checked for the antibacterial activity against both Gram positive and Gram negative bacteria. The characterization studies clearly revealed the formation and synthesis of SNPs which also showed the inhibitory activity on the tested bacteria.  SNPs of Excoecaria agallocha fruit showed higher zone of inhibition against Micrococcus luteus, Arthrobacter protophormiae, Rhodococcus rhodochrous, Bacillus subtilis, Alcaligens faecalis, Enterobacter aerogenes, Proteus mirabilis and Salmonella enterica when compared to that of standard antibiotic, Streptomycin

REAL TIME TRAFFIC PREDICTION FOR PHYSICAL STORES

A traffic predictor system can be used to predict customer traffic to physical stores. The system receives data describing search queries from a population of users. The system identifies intents of the population of users based on the search queries from the population of users. The intents may include local intent, i.e., intent to visit a physical store, and/or a product intent, i.e., intent to obtain a product. The system determines probabilities that the identified intents will lead to customers visiting the store. Subsequently, the system can generate traffic predictions for stores based on the determined probabilities for the identified intents

C-SPADE : a web-tool for interactive analysis and visualization of drug screening experiments through compound-specific bioactivity dendrograms

The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds' multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at http://cspade.fimm.fi/.Peer reviewe

Optimal Energy Shaping Control for a Backdrivable Hip Exoskeleton

Task-dependent controllers widely used in exoskeletons track predefined trajectories, which overly constrain the volitional motion of individuals with remnant voluntary mobility. Energy shaping, on the other hand, provides task-invariant assistance by altering the human body's dynamic characteristics in the closed loop. While human-exoskeleton systems are often modeled using Euler-Lagrange equations, in our previous work we modeled the system as a port-controlled-Hamiltonian system, and a task-invariant controller was designed for a knee-ankle exoskeleton using interconnection-damping assignment passivity-based control. In this paper, we extend this framework to design a controller for a backdrivable hip exoskeleton to assist multiple tasks. A set of basis functions that contains information of kinematics is selected and corresponding coefficients are optimized, which allows the controller to provide torque that fits normative human torque for different activities of daily life. Human-subject experiments with two able-bodied subjects demonstrated the controller's capability to reduce muscle effort across different tasks

1-Hour Post-OGTT Glucose Improves the Early Prediction of Type 2 Diabetes by Clinical and Metabolic Markers

Context: Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c). Objective: To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT). Design and Setting: We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes. Results: The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour PG according to DeLong test P value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker. Conclusions: The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability.Peer reviewe

Low latency modeling of temporal contexts for speech recognition

This thesis focuses on the development of neural network acoustic models for large vocabulary continuous speech recognition (LVCSR) to satisfy the design goals of low latency and low computational complexity. Low latency enables online speech recognition; and low computational complexity helps reduce the computational cost both during training and inference. Long span sequential dependencies and sequential distortions in the input vector sequence are a major challenge in acoustic modeling. Recurrent neural networks have been shown to effectively model these dependencies. Specifically, bidirectional long short term memory (BLSTM) networks, provide state-of-the-art performance across several LVCSR tasks. However the deployment of bidirectional models for online LVCSR is non-trivial due to their large latency; and unidirectional LSTM models are typically preferred. In this thesis we explore the use of hierarchical temporal convolution to model long span temporal dependencies. We propose a sub-sampled variant of these temporal convolution neural networks, termed time-delay neural networks (TDNNs). These sub-sampled TDNNs reduce the computation complexity by ~5x, compared to TDNNs, during frame randomized pre-training. These models are shown to be effective in modeling long-span temporal contexts, however there is a performance gap compared to (B)LSTMs. As recent advancements in acoustic model training have eliminated the need for frame randomized pre-training we modify the TDNN architecture to use higher sampling rates, as the increased computation can be amortized over the sequence. These variants of sub- sampled TDNNs provide performance superior to unidirectional LSTM networks, while also affording a lower real time factor (RTF) during inference. However we show that the BLSTM models outperform both the TDNN and LSTM models. We propose a hybrid architecture interleaving temporal convolution and LSTM layers which is shown to outperform the BLSTM models. Further we improve these BLSTM models by using higher frame rates at lower layers and show that the proposed TDNN- LSTM model performs similar to these superior BLSTM models, while reducing the overall latency to 200 ms. Finally we describe an online system for reverberation robust ASR, using the above described models in conjunction with other data augmentation techniques like reverberation simulation, which simulates far-field environments, and volume perturbation, which helps tackle volume variation even without gain normalization

Towards Fine-Grained Localization of Privacy Behaviors

Mobile applications are required to give privacy notices to users when they collect or share personal information. Creating consistent and concise privacy notices can be a challenging task for developers. Previous work has attempted to help developers create privacy notices through a questionnaire or predefined templates. In this paper, we propose a novel approach and a framework, called PriGen, that extends these prior work. PriGen uses static analysis to identify Android applications' code segments that process sensitive information (i.e. permission-requiring code segments) and then leverages a Neural Machine Translation model to translate them into privacy captions. We present the initial evaluation of our translation task for ~300,000 code segments