Machine learning methods for prediction of disulphide bonding states of cysteine residues in proteins

The goal of this thesis work is to develop a computational method based on machine learning techniques for predicting disulfide-bonding states of cysteine residues in proteins, which is a sub-problem of a bigger and yet unsolved problem of protein structure prediction. Improvement in the prediction of disulfide bonding states of cysteine residues will help in putting a constraint in the three dimensional (3D) space of the respective protein structure, and thus will eventually help in the prediction of 3D structure of proteins. Results of this work will have direct implications in site-directed mutational studies of proteins, proteins engineering and the problem of protein folding. We have used a combination of Artificial Neural Network (ANN) and Hidden Markov Model (HMM), the so-called Hidden Neural Network (HNN) as a machine learning technique to develop our prediction method. By using different global and local features of proteins (specifically profiles, parity of cysteine residues, average cysteine conservation, correlated mutation, sub-cellular localization, and signal peptide) as inputs and considering Eukaryotes and Prokaryotes separately we have reached to a remarkable accuracy of 94% on cysteine basis for both Eukaryotic and Prokaryotic datasets, and an accuracy of 90% and 93% on protein basis for Eukaryotic dataset and Prokaryotic dataset respectively. These accuracies are best so far ever reached by any existing prediction methods, and thus our prediction method has outperformed all the previously developed approaches and therefore is more reliable. Most interesting part of this thesis work is the differences in the prediction performances of Eukaryotes and Prokaryotes at the basic level of input coding when ‘profile’ information was given as input to our prediction method. And one of the reasons for this we discover is the difference in the amino acid composition of the local environment of bonded and free cysteine residues in Eukaryotes and Prokaryotes. Eukaryotic bonded cysteine examples have a ‘symmetric-cysteine-rich’ environment, where as Prokaryotic bonded examples lack it.

Machine-learning methods for structure prediction of β-barrel membrane proteins

Different types of proteins exist with diverse functions that are essential for living organisms. An important class of proteins is represented by transmembrane proteins which are specifically designed to be inserted into biological membranes and devised to perform very important functions in the cell such as cell communication and active transport across the membrane. Transmembrane β-barrels (TMBBs) are a sub-class of membrane proteins largely under-represented in structure databases because of the extreme difficulty in experimental structure determination. For this reason, computational tools that are able to predict the structure of TMBBs are needed. In this thesis, two computational problems related to TMBBs were addressed: the detection of TMBBs in large datasets of proteins and the prediction of the topology of TMBB proteins. Firstly, a method for TMBB detection was presented based on a novel neural network framework for variable-length sequence classification. The proposed approach was validated on a non-redundant dataset of proteins. Furthermore, we carried-out genome-wide detection using the entire Escherichia coli proteome. In both experiments, the method significantly outperformed other existing state-of-the-art approaches, reaching very high PPV (92%) and MCC (0.82). Secondly, a method was also introduced for TMBB topology prediction. The proposed approach is based on grammatical modelling and probabilistic discriminative models for sequence data labeling. The method was evaluated using a newly generated dataset of 38 TMBB proteins obtained from high-resolution data in the PDB. Results have shown that the model is able to correctly predict topologies of 25 out of 38 protein chains in the dataset. When tested on previously released datasets, the performances of the proposed approach were measured as comparable or superior to the current state-of-the-art of TMBB topology prediction.

Le tecniche di machine learning per il trattamento della sindrome dell'arto fantasma

Questo elaborato ha come scopo quello di analizzare ed esaminare una patologia oggetto di attiva ricerca scientifica, la sindrome dell’arto fantasma o phantom limb pain: tracciando la storia delle terapie più utilizzate per la sua attenuazione, si è giunti ad analizzarne lo stato dell’arte. Consapevoli che la sindrome dell’arto fantasma costituisce, oltre che un disturbo per chi la prova, uno strumento assai utile per l’analisi delle attività nervose del segmento corporeo superstite (moncone), si è svolta un’attività al centro Inail di Vigorso di Budrio finalizzata a rilevare segnali elettrici provenienti dai monconi superiori dei pazienti che hanno subito un’amputazione. Avendo preliminarmente trattato l’argomento “Machine learning” per raggiungere una maggiore consapevolezza delle potenzialità dell’apprendimento automatico, si sono analizzate la attività neuronali dei pazienti mentre questi muovevano il loro arto fantasma per riuscire a settare nuove tipologie di protesi mobili in base ai segnali ricevuti dal moncone.

Machine Learning applicato al Web Semantico: Statistical Relational Learning vs Tensor Factorization

Obiettivo della tesi è analizzare e testare i principali approcci di Machine Learning applicabili in contesti semantici, partendo da algoritmi di Statistical Relational Learning, quali Relational Probability Trees, Relational Bayesian Classifiers e Relational Dependency Networks, per poi passare ad approcci basati su fattorizzazione tensori, in particolare CANDECOMP/PARAFAC, Tucker e RESCAL.

Predicting CMS datasets popularity with machine learning

In CMS è stato lanciato un progetto di Data Analytics e, all’interno di esso, un’attività specifica pilota che mira a sfruttare tecniche di Machine Learning per predire la popolarità dei dataset di CMS. Si tratta di un’osservabile molto delicata, la cui eventuale predizione premetterebbe a CMS di costruire modelli di data placement più intelligenti, ampie ottimizzazioni nell’uso dello storage a tutti i livelli Tiers, e formerebbe la base per l’introduzione di un solito sistema di data management dinamico e adattivo. Questa tesi descrive il lavoro fatto sfruttando un nuovo prototipo pilota chiamato DCAFPilot, interamente scritto in python, per affrontare questa sfida.

Big data, nosql e machine learning: un'applicazione di prediction e recommendation basata sulle api di Amazon

In questa tesi sono stati introdotti e studiati i Big Data, dando particolare importanza al mondo NoSQL, approfondendo MongoDB, e al mondo del Machine Learning, approfondendo PredictionIO. Successivamente è stata sviluppata un'applicazione attraverso l'utilizzo di tecnologie web, nodejs, node-webkit e le tecnologie approfondite prima. L'applicazione utilizza l'interpolazione polinomiale per predirre il prezzo di un bene salvato nello storico presente su MongoDB. Attraverso PredictionIO, essa analizza il comportamento degli altri utenti consigliando dei prodotti per l'acquisto. Infine è stata effetuata un'analisi dei risultati dell'errore prodotto dall'interpolazione.

Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm

Abstract Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy gamma radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to gamma radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2'-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release.

Combining Wireless Sensor Networks and Machine Learning for Flash Flood Nowcasting

This paper addresses an investigation with machine learning (ML) classification techniques to assist in the problem of flash flood now casting. We have been attempting to build a Wireless Sensor Network (WSN) to collect measurements from a river located in an urban area. The machine learning classification methods were investigated with the aim of allowing flash flood now casting, which in turn allows the WSN to give alerts to the local population. We have evaluated several types of ML taking account of the different now casting stages (i.e. Number of future time steps to forecast). We have also evaluated different data representation to be used as input of the ML techniques. The results show that different data representation can lead to results significantly better for different stages of now casting.

Fast Prediction of Femoral Biomechanics Using Supervised Machine Learning and Statistical Shape Modeling

Finite element (FE) analysis is an important computational tool in biomechanics. However, its adoption into clinical practice has been hampered by its computational complexity and required high technical competences for clinicians. In this paper we propose a supervised learning approach to predict the outcome of the FE analysis. We demonstrate our approach on clinical CT and X-ray femur images for FE predictions ( FEP), with features extracted, respectively, from a statistical shape model and from 2D-based morphometric and density information. Using leave-one-out experiments and sensitivity analysis, comprising a database of 89 clinical cases, our method is capable of predicting the distribution of stress values for a walking loading condition with an average correlation coefficient of 0.984 and 0.976, for CT and X-ray images, respectively. These findings suggest that supervised learning approaches have the potential to leverage the clinical integration of mechanical simulations for the treatment of musculoskeletal conditions.

Comparison of machine learning approaches and statistical methods for estimation of airborne chemical exposures

Accurate quantitative estimation of exposure using retrospective data has been one of the most challenging tasks in the exposure assessment field. To improve these estimates, some models have been developed using published exposure databases with their corresponding exposure determinants. These models are designed to be applied to reported exposure determinants obtained from study subjects or exposure levels assigned by an industrial hygienist, so quantitative exposure estimates can be obtained. ^ In an effort to improve the prediction accuracy and generalizability of these models, and taking into account that the limitations encountered in previous studies might be due to limitations in the applicability of traditional statistical methods and concepts, the use of computer science- derived data analysis methods, predominantly machine learning approaches, were proposed and explored in this study. ^ The goal of this study was to develop a set of models using decision trees/ensemble and neural networks methods to predict occupational outcomes based on literature-derived databases, and compare, using cross-validation and data splitting techniques, the resulting prediction capacity to that of traditional regression models. Two cases were addressed: the categorical case, where the exposure level was measured as an exposure rating following the American Industrial Hygiene Association guidelines and the continuous case, where the result of the exposure is expressed as a concentration value. Previously developed literature-based exposure databases for 1,1,1 trichloroethane, methylene dichloride and, trichloroethylene were used. ^ When compared to regression estimations, results showed better accuracy of decision trees/ensemble techniques for the categorical case while neural networks were better for estimation of continuous exposure values. Overrepresentation of classes and overfitting were the main causes for poor neural network performance and accuracy. Estimations based on literature-based databases using machine learning techniques might provide an advantage when they are applied to other methodologies that combine `expert inputs' with current exposure measurements, like the Bayesian Decision Analysis tool. The use of machine learning techniques to more accurately estimate exposures from literature-based exposure databases might represent the starting point for the independence from the expert judgment.^

Hybrid Approach Combining Machine Learning and a Rule-Based Expert System for Text Categorization

This paper discusses a novel hybrid approach for text categorization that combines a machine learning algorithm, which provides a base model trained with a labeled corpus, with a rule-based expert system, which is used to improve the results provided by the previous classifier, by filtering false positives and dealing with false negatives. The main advantage is that the system can be easily fine-tuned by adding specific rules for those noisy or conflicting categories that have not been successfully trained. We also describe an implementation based on k-Nearest Neighbor and a simple rule language to express lists of positive, negative and relevant (multiword) terms appearing in the input text. The system is evaluated in several scenarios, including the popular Reuters-21578 news corpus for comparison to other approaches, and categorization using IPTC metadata, EUROVOC thesaurus and others. Results show that this approach achieves a precision that is comparable to top ranked methods, with the added value that it does not require a demanding human expert workload to train

Regularization for sparsity in statistical analysis and machine learning

Pragmatism is the leading motivation of regularization. We can understand regularization as a modification of the maximum-likelihood estimator so that a reasonable answer could be given in an unstable or ill-posed situation. To mention some typical examples, this happens when fitting parametric or non-parametric models with more parameters than data or when estimating large covariance matrices. Regularization is usually used, in addition, to improve the bias-variance tradeoff of an estimation. Then, the definition of regularization is quite general, and, although the introduction of a penalty is probably the most popular type, it is just one out of multiple forms of regularization. In this dissertation, we focus on the applications of regularization for obtaining sparse or parsimonious representations, where only a subset of the inputs is used. A particular form of regularization, L1-regularization, plays a key role for reaching sparsity. Most of the contributions presented here revolve around L1-regularization, although other forms of regularization are explored (also pursuing sparsity in some sense). In addition to present a compact review of L1-regularization and its applications in statistical and machine learning, we devise methodology for regression, supervised classification and structure induction of graphical models. Within the regression paradigm, we focus on kernel smoothing learning, proposing techniques for kernel design that are suitable for high dimensional settings and sparse regression functions. We also present an application of regularized regression techniques for modeling the response of biological neurons. Supervised classification advances deal, on the one hand, with the application of regularization for obtaining a na¨ıve Bayes classifier and, on the other hand, with a novel algorithm for brain-computer interface design that uses group regularization in an efficient manner. Finally, we present a heuristic for inducing structures of Gaussian Bayesian networks using L1-regularization as a filter. El pragmatismo es la principal motivación de la regularización. Podemos entender la regularización como una modificación del estimador de máxima verosimilitud, de tal manera que se pueda dar una respuesta cuando la configuración del problema es inestable. A modo de ejemplo, podemos mencionar el ajuste de modelos paramétricos o no paramétricos cuando hay más parámetros que casos en el conjunto de datos, o la estimación de grandes matrices de covarianzas. Se suele recurrir a la regularización, además, para mejorar el compromiso sesgo-varianza en una estimación. Por tanto, la definición de regularización es muy general y, aunque la introducción de una función de penalización es probablemente el método más popular, éste es sólo uno de entre varias posibilidades. En esta tesis se ha trabajado en aplicaciones de regularización para obtener representaciones dispersas, donde sólo se usa un subconjunto de las entradas. En particular, la regularización L1 juega un papel clave en la búsqueda de dicha dispersión. La mayor parte de las contribuciones presentadas en la tesis giran alrededor de la regularización L1, aunque también se exploran otras formas de regularización (que igualmente persiguen un modelo disperso). Además de presentar una revisión de la regularización L1 y sus aplicaciones en estadística y aprendizaje de máquina, se ha desarrollado metodología para regresión, clasificación supervisada y aprendizaje de estructura en modelos gráficos. Dentro de la regresión, se ha trabajado principalmente en métodos de regresión local, proponiendo técnicas de diseño del kernel que sean adecuadas a configuraciones de alta dimensionalidad y funciones de regresión dispersas. También se presenta una aplicación de las técnicas de regresión regularizada para modelar la respuesta de neuronas reales. Los avances en clasificación supervisada tratan, por una parte, con el uso de regularización para obtener un clasificador naive Bayes y, por otra parte, con el desarrollo de un algoritmo que usa regularización por grupos de una manera eficiente y que se ha aplicado al diseño de interfaces cerebromáquina. Finalmente, se presenta una heurística para inducir la estructura de redes Bayesianas Gaussianas usando regularización L1 a modo de filtro.