A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

Detecting anomalous events at railway level crossings

Collisions between pedestrians and vehicles continue to be a major problem throughout the world. Pedestrians trying to cross roads and railway tracks without any caution are often highly susceptible to collisions with vehicles and trains. Continuous financial, human and other losses have prompted transport related organizations to come up with various solutions addressing this issue. However, the quest for new and significant improvements in this area is still ongoing. This work addresses this issue by building a general framework using computer vision techniques to automatically monitor pedestrian movements in such high-risk areas to enable better analysis of activity, and the creation of future alerting strategies. As a result of rapid development in the electronics and semi-conductor industry there is extensive deployment of CCTV cameras in public places to capture video footage. This footage can then be used to analyse crowd activities in those particular places. This work seeks to identify the abnormal behaviour of individuals in video footage. In this work we propose using a Semi-2D Hidden Markov Model (HMM), Full-2D HMM and Spatial HMM to model the normal activities of people. The outliers of the model (i.e. those observations with insufficient likelihood) are identified as abnormal activities. Location features, flow features and optical flow textures are used as the features for the model. The proposed approaches are evaluated using the publicly available UCSD datasets, and we demonstrate improved performance using a Semi-2D Hidden Markov Model compared to other state of the art methods. Further we illustrate how our proposed methods can be applied to detect anomalous events at rail level crossings.

An evaluation of different features and learning models for anomalous event detection

The huge amount of CCTV footage available makes it very burdensome to process these videos manually through human operators. This has made automated processing of video footage through computer vision technologies necessary. During the past several years, there has been a large effort to detect abnormal activities through computer vision techniques. Typically, the problem is formulated as a novelty detection task where the system is trained on normal data and is required to detect events which do not fit the learned ‘normal’ model. There is no precise and exact definition for an abnormal activity; it is dependent on the context of the scene. Hence there is a requirement for different feature sets to detect different kinds of abnormal activities. In this work we evaluate the performance of different state of the art features to detect the presence of the abnormal objects in the scene. These include optical flow vectors to detect motion related anomalies, textures of optical flow and image textures to detect the presence of abnormal objects. These extracted features in different combinations are modeled using different state of the art models such as Gaussian mixture model(GMM) and Semi- 2D Hidden Markov model(HMM) to analyse the performances. Further we apply perspective normalization to the extracted features to compensate for perspective distortion due to the distance between the camera and objects of consideration. The proposed approach is evaluated using the publicly available UCSD datasets and we demonstrate improved performance compared to other state of the art methods.

Computational methods for the prediction of the structure and interactions of coiled-coil peptides

The past several years have seen significant advances in the development of computational methods for the prediction of the structure and interactions of coiled-coil peptides. These methods are generally based on pairwise correlations of amino acids, helical propensity, thermal melts and the energetics of sidechain interactions, as well as statistical patterns based on Hidden Markov Model (HMM) and Support Vector Machine (SVM) techniques. These methods are complemented by a number of public databases that contain sequences, motifs, domains and other details of coiled-coil structures identified by various algorithms. Some of these computational methods have been developed to make predictions of coiled-coil structure on the basis of sequence information; however, structural predictions of the oligomerisation state of these peptides still remains largely an open question due to the dynamic behaviour of these molecules. This review focuses on existing in silico methods for the prediction of coiled-coil peptides of functional importance using sequence and/or three-dimensional structural data.

Joint evaluation of multiple speech patterns for speech recognition and training

We are addressing the novel problem of jointly evaluating multiple speech patterns for automatic speech recognition and training. We propose solutions based on both the non-parametric dynamic time warping (DTW) algorithm, and the parametric hidden Markov model (HMM). We show that a hybrid approach is quite effective for the application of noisy speech recognition. We extend the concept to HMM training wherein some patterns may be noisy or distorted. Utilizing the concept of ``virtual pattern'' developed for joint evaluation, we propose selective iterative training of HMMs. Evaluating these algorithms for burst/transient noisy speech and isolated word recognition, significant improvement in recognition accuracy is obtained using the new algorithms over those which do not utilize the joint evaluation strategy.

Deploying speaker verification techniques to vision-based RPA detect and avoid

Detect and Avoid (DAA) technology is widely acknowledged as a critical enabler for unsegregated Remote Piloted Aircraft (RPA) operations, particularly Beyond Visual Line of Sight (BVLOS). Image-based DAA, in the visible spectrum, is a promising technological option for addressing the challenges DAA presents. Two impediments to progress for this approach are the scarcity of available video footage to train and test algorithms, in conjunction with testing regimes and specifications which facilitate repeatable, statistically valid, performance assessment. This paper includes three key contributions undertaken to address these impediments. In the first instance, we detail our progress towards the creation of a large hybrid collision and near-collision encounter database. Second, we explore the suitability of techniques employed by the biometric research community (Speaker Verification and Language Identification), for DAA performance optimisation and assessment. These techniques include Detection Error Trade-off (DET) curves, Equal Error Rates (EER), and the Detection Cost Function (DCF). Finally, the hybrid database and the speech-based techniques are combined and employed in the assessment of a contemporary, image based DAA system. This system includes stabilisation, morphological filtering and a Hidden Markov Model (HMM) temporal filter.

Multi-Pattern Viterbi Algorithm for joint decoding of multiple speech patterns

Joint decoding of multiple speech patterns so as to improve speech recognition performance is important, especially in the presence of noise. In this paper, we propose a Multi-Pattern Viterbi algorithm (MPVA) to jointly decode and recognize multiple speech patterns for automatic speech recognition (ASR). The MPVA is a generalization of the Viterbi Algorithm to jointly decode multiple patterns given a Hidden Markov Model (HMM). Unlike the previously proposed two stage Constrained Multi-Pattern Viterbi Algorithm (CMPVA),the MPVA is a single stage algorithm. MPVA has the advantage that it cart be extended to connected word recognition (CWR) and continuous speech recognition (CSR) problems. MPVA is shown to provide better speech recognition performance than the earlier techniques: using only two repetitions of noisy speech patterns (-5 dB SNR, 10% burst noise), the word error rate using MPVA decreased by 28.5%, when compared to using individual decoding. (C) 2010 Elsevier B.V. All rights reserved.

Speech Recognition of Malayalam Numbers

Digit speech recognition is important in many applications such as automatic data entry, PIN entry, voice dialing telephone, automated banking system, etc. This paper presents speaker independent speech recognition system for Malayalam digits. The system employs Mel frequency cepstrum coefficient (MFCC) as feature for signal processing and Hidden Markov model (HMM) for recognition. The system is trained with 21 male and female voices in the age group of 20 to 40 years and there was 98.5% word recognition accuracy (94.8% sentence recognition accuracy) on a test set of continuous digit recognition task.

Automated Transcription System for Malayalam Language

Malayalam is one of the 22 scheduled languages in India with more than 130 million speakers. This paper presents a report on the development of a speaker independent, continuous transcription system for Malayalam. The system employs Hidden Markov Model (HMM) for acoustic modeling and Mel Frequency Cepstral Coefficient (MFCC) for feature extraction. It is trained with 21 male and female speakers in the age group ranging from 20 to 40 years. The system obtained a word recognition accuracy of 87.4% and a sentence recognition accuracy of 84%, when tested with a set of continuous speech data.

Connected digit speech recognition system for Malayalam language

A connected digit speech recognition is important in many applications such as automated banking system, catalogue-dialing, automatic data entry, automated banking system, etc. This paper presents an optimum speaker-independent connected digit recognizer forMalayalam language. The system employs Perceptual Linear Predictive (PLP) cepstral coefficient for speech parameterization and continuous density Hidden Markov Model (HMM) in the recognition process. Viterbi algorithm is used for decoding. The training data base has the utterance of 21 speakers from the age group of 20 to 40 years and the sound is recorded in the normal office environment where each speaker is asked to read 20 set of continuous digits. The system obtained an accuracy of 99.5 % with the unseen data.

Predição computacional de promotores em Xanthomonas axonopodis pv. citri

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise de técnicas de reconhecimento de padrões para a identificação biométrica de usuários em aplicações WEB Utilizando faces a partir de vídeos

Pós-graduação em Ciência da Computação - IBILCE

Desenvolvimento de recursos para a construção de um sistema texto-fala para o português brasileiro

Sistema Texto-Fala (TTS) é atualmente uma tecnologia madura que é utilizada em muitas aplicações. Alguns módulos de um sistema TTS são dependentes do idioma e, enquanto existem muitos recursos disponíveis para a língua inglesa, os recursos para alguns idiomas ainda são limitados. Este trabalho descreve o desenvolvimento de um sistema TTS completo para português brasileiro (PB), o qual também apresenta os recursos já disponíveis. O sistema usa a plataforma MARY e o processo de síntese da voz é baseado em cadeias escondidas de Markov (HMM). Algumas das contribuições deste trabalho consistem na implementação de silabação, determinação da sílaba tônica e conversão grafema-fonema (G2P). O trabalho também descreve as etapas para a organização dos recursos desenvolvidos e a criação de uma voz em PB junto ao MARY. Estes recursos estão disponíveis e facilita a pesquisa na normalização de texto e síntese baseada em HMM par o PB.

Ab initio protein folding simulations using atomic burials as informational intermediates between sequence and structure

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Design and implementation of bioinformatics tools for large scale genome annotation

The continuous increase of genome sequencing projects produced a huge amount of data in the last 10 years: currently more than 600 prokaryotic and 80 eukaryotic genomes are fully sequenced and publically available. However the sole sequencing process of a genome is able to determine just raw nucleotide sequences. This is only the first step of the genome annotation process that will deal with the issue of assigning biological information to each sequence. The annotation process is done at each different level of the biological information processing mechanism, from DNA to protein, and cannot be accomplished only by in vitro analysis procedures resulting extremely expensive and time consuming when applied at a this large scale level. Thus, in silico methods need to be used to accomplish the task. The aim of this work was the implementation of predictive computational methods to allow a fast, reliable, and automated annotation of genomes and proteins starting from aminoacidic sequences. The first part of the work was focused on the implementation of a new machine learning based method for the prediction of the subcellular localization of soluble eukaryotic proteins. The method is called BaCelLo, and was developed in 2006. The main peculiarity of the method is to be independent from biases present in the training dataset, which causes the over‐prediction of the most represented examples in all the other available predictors developed so far. This important result was achieved by a modification, made by myself, to the standard Support Vector Machine (SVM) algorithm with the creation of the so called Balanced SVM. BaCelLo is able to predict the most important subcellular localizations in eukaryotic cells and three, kingdom‐specific, predictors were implemented. In two extensive comparisons, carried out in 2006 and 2008, BaCelLo reported to outperform all the currently available state‐of‐the‐art methods for this prediction task. BaCelLo was subsequently used to completely annotate 5 eukaryotic genomes, by integrating it in a pipeline of predictors developed at the Bologna Biocomputing group by Dr. Pier Luigi Martelli and Dr. Piero Fariselli. An online database, called eSLDB, was developed by integrating, for each aminoacidic sequence extracted from the genome, the predicted subcellular localization merged with experimental and similarity‐based annotations. In the second part of the work a new, machine learning based, method was implemented for the prediction of GPI‐anchored proteins. Basically the method is able to efficiently predict from the raw aminoacidic sequence both the presence of the GPI‐anchor (by means of an SVM), and the position in the sequence of the post‐translational modification event, the so called ω‐site (by means of an Hidden Markov Model (HMM)). The method is called GPIPE and reported to greatly enhance the prediction performances of GPI‐anchored proteins over all the previously developed methods. GPIPE was able to predict up to 88% of the experimentally annotated GPI‐anchored proteins by maintaining a rate of false positive prediction as low as 0.1%. GPIPE was used to completely annotate 81 eukaryotic genomes, and more than 15000 putative GPI‐anchored proteins were predicted, 561 of which are found in H. sapiens. In average 1% of a proteome is predicted as GPI‐anchored. A statistical analysis was performed onto the composition of the regions surrounding the ω‐site that allowed the definition of specific aminoacidic abundances in the different considered regions. Furthermore the hypothesis that compositional biases are present among the four major eukaryotic kingdoms, proposed in literature, was tested and rejected. All the developed predictors and databases are freely available at: BaCelLo http://gpcr.biocomp.unibo.it/bacello eSLDB http://gpcr.biocomp.unibo.it/esldb GPIPE http://gpcr.biocomp.unibo.it/gpipe