A new gene inventory of the ubiquitin and ubiquitin-like conjugation pathways in Giardia intestinalis

BACKGROUND Ubiquitin (Ub) and Ub-like proteins (Ub-L) are critical regulators of complex cellular processes such as the cell cycle, DNA repair, transcription, chromatin remodeling, signal translation, and protein degradation. Giardia intestinalis possesses an experimentally proven Ub-conjugation system; however, a limited number of enzymes involved in this process were identified using basic local alignment search tool (BLAST). This is due to the limitations of BLAST's ability to identify homologous functional regions when similarity between the sequences dips to < 30%. In addition Ub-Ls and their conjugating enzymes have not been fully elucidated in Giardia. OBJETIVE To identify the enzymes involved in the Ub and Ub-Ls conjugation processes using intelligent systems based on the hidden Markov models (HMMs). METHODS We performed an HMM search of functional Pfam domains found in the key enzymes of these pathways in Giardia's proteome. Each open reading frame identified was analysed by sequence homology, domain architecture, and transcription levels. FINDINGS We identified 118 genes, 106 of which corresponded to the ubiquitination process (Ub, E1, E2, E3, and DUB enzymes). The E3 ligase group was the largest group with 82 members; 71 of which harbored a characteristic RING domain. Four Ub-Ls were identified and the conjugation enzymes for NEDD8 and URM1 were described for first time. The 3D model for Ub-Ls displayed the β-grasp fold typical. Furthermore, our sequence analysis for the corresponding activating enzymes detected the essential motifs required for conjugation. MAIN CONCLUSIONS Our findings highlight the complexity of Giardia's Ub-conjugation system, which is drastically different from that previously reported, and provides evidence for the presence of NEDDylation and URMylation enzymes in the genome and transcriptome of G. intestinalis.

Assessment of Dysarthria Using One-Word Speech Recognition with Hidden Markov Models

BACKGROUND: The gold standard in dysarthria assessment involves subjective analysis by a speech–language pathologist (SLP). We aimed to investigate the feasibility of dysarthria assessment using automatic speech recognition. METHODS: We developed an automatic speech recognition based software to assess dysarthria severity using hidden Markov models (HMMs). Word-specific HMMs were trained using the utterances from one hundred healthy individuals. Twenty-eight patients with dysarthria caused by neurological disorders, including stroke, traumatic brain injury, and Parkinson's disease were participated and their utterances were recorded. The utterances of 37 words from the Assessment of Phonology and Articulation for Children test were recorded in a quiet control booth in both groups. Patients were asked to repeat the recordings for evaluating the test–retest reliability. Patients' utterances were evaluated by two experienced SLPs, and the consonant production accuracy was calculated as a measure of dysarthria severity. The trained HMMs were also employed to evaluate the patients' utterances by calculating the averaged log likelihood (aLL) as the fitness of the spoken word to the word-specific HMM. RESULTS: The consonant production accuracy reported by the SLPs strongly correlated (r = 0.808) with the aLL, and the aLL showed excellent test–retest reliability (intraclass correlation coefficient, 0.964). CONCLUSION: This leads to the conclusion that dysarthria assessment using a one-word speech recognition system based on word-specific HMMs is feasible in neurological disorders.

Detección Automática y Clasificación de Eventos en Sonidos Cardiopulmonares de Sujetos Saludables / Automatic Detection and Classification of Cardiopulmonary Events

Resumen: La auscultación de señales basada en un estetoscopio estándar y/o electrónico no solo incluye sonidos internos del cuerpo, también incluye frecuentemente ruido externo de interferencia con componentes en el mismo rango. Esta forma de examinar es incluso afectada por los umbrales auditivos variantes de los profesionales de la salud y el grado de experiencia en reconocimiento de indicadores peculiares. Además, los resultados son a menudo caracterizados en términos cualitativos descriptivos sujetos a interpretaciones individuales. Para direccionar esta preocupación, los estudios presentados en este artículo contienen un procesamiento concurrente de las componentes dominantes de sonidos del corazón (HS) y del pulmón (HS), y una etapa de acondicionamiento que incluye la reducción de HS presente en señales LS. Específicamente, la transformada de Hilbert fue una técnica de caracterización para HS. En el caso de señales enfocadas a LS, las técnicas de detección de actividad de voz y el cálculo de umbrales de algunos componentes de los vectores acústicos de Coeficientes Cepstrales en Frecuencia Mel (MFCC), fueron útiles en la caracterización de eventos acústicos asociados. Las fases de inspiración y expiración fueron diferenciadas por medio de la sexta componente de MFCC. Con el fin de evaluar la eficiencia de esta aproximación, proponemos los Modelos Ocultos de Markov con Modelos Mesclados Gaussianos (HMM-GMM). Los resultados utilizando esta forma de detección son superiores cuando se desarrolla la clasificación con modelos HMM-GMM, la cual refleja las ventajas de la forma de detección cuantificable y clasificación sobre la aproximación clínica tradicional.

Abstract: A standard and/or electronic stethoscope based auscultatory signals include not only the internal sounds of the body but also interfering external noise often with similar frequency components. This form of examination is also affected by varying thresholds of clinical practitioner's hearing and degree of experience in recognition of peculiar auscultatory indicators. Further, the results are often characterized in qualitative descriptive terms subject to individual's interpretation. To address these concerns, presented studies include concurrent processing of dominant heart (HS) and lung (LS) sounds components and a conditioning stage involving HS presence reduction within LS focused signals. Specifically as determined, the Hilbert transform was a technique of choice in HS characterization. In the case of LS focused signals, the speech activity detection techniques (VAD) and the thresholds calculation of some components of acoustic vectors of Cepstral Coefficients in Mel Frequency (MFCC), were useful in characterization of associated acoustic events. The phases of inspiration and expiration were differentiated by means of the sixth component of MFCC. In order to evaluate the efficiency of this approach, we propose Hidden Markov Models with Mixed Gaussian Models (HMM-GMM). The results utilizing this form of detection are superior when performing classification with HMM-GMM models, which reflect the advantages of presented form of quantifiable detection and classification over traditional clinical approach.

Determinación del Tamaño Óptimo de Modelos HMM-GMM para Clasificación de las Señales Bioacústicas / Determining optimal size of HMM-GMM models to classify bio-acoustic signal

Resumen Este artículo está relacionado con el análisis y la propuesta de una arquitectura HMM-GMM para clasificación de señales HS y LS, haciendo un énfasis en el tamaño del modelo. Actualmente, las enfermedades respiratorias y cardiovasculares son un problema a nivel mundial y con una alta mortandad, esto podría ser disminuido mediante un diagnóstico temprano y objetivo; las herramientas digitales y el empleo de reconocimiento de patrones ampliarían las perspectivas de aplicación. Particularmente, aquí se demuestra que los modelos HMM-GMM son eficientes para consultorios de atención primaria, así mismo los extractores de características tales como MFCC y Cuantiles mejoran la tarea de clasificación. Si bien la visualización con siluetas, dendrogramas y algoritmos tales como BIC no son concluyentes cuando se aplican GMM's, no obstante sí fue el punto de partida para dimensionar el tamaño del modelo, disminuyendo la cantidad de experimentos con distintos tamaños del mismo. Adicionalmente, se constata que la estructura de señales normales HS y LS cambian cuando hay patologías y permite la clasificación aplicando MFCC o Cuantiles. Además, se observa que con una gran cantidad de datos se podrían obtener modelos más robustos y adaptados, pero esto no es una limitante para el cálculo de los modelos.

Abstract This paper demonstrates the analysis and proposed HMM-GMM models architecture to classify heart and lung sounds (HS and LS) signals emphasizing the model size optimization. Respiratory and cardiovascular diseases continue to represent one of the major worldwide healthcare problems associated with a liigli mortality rate, wliicli can be reduced by an early and effective diagnosis; in this context, the use of digital tools utilizing signal pattern recognition allows efficient screening for abnormalities and their quantitative assessment. In particular, the HMM-GMM models demonstrated their efficiency in normal and traditionally noisy environments in light of very low intensities of these auscultation signals used as diagnostic indicators. Furthermore, applied MFCC and Quantiles feature extractors improve overall classification. While characterization with silhouettes, dendrograms and algorithms such as BIC was inconclusive when GMM was applied, however they were useful as a starting point in the determination of a size of the model as it allowed a reduction in the number of iterations considering different model size. In addition one can note that application of MFCC or Quantiles allowed differentiating the characteristics of normal HS and LS from those associated with pathological conditions. Furthermore, it was observed that a large amount of data leads to more robust and adapted models, but does not limit the calculation demand. Overall, this approach may enhance efficiency and precision of the diagnostic screening for abnormal auscultation indicators.

Clasificación de eritrocitos empleando modelos ocultos de Márkov / Red Blood cell classification with hidden Markov models

Se realiza un estudio del desempeño de los modelos ocultos de Márkov (HMM) en la clasificación morfológica supervisada de eritrocitos en muestras de sangre periférica de pacientes con anemia drepanocítica. Los contornos se representan de forma novedosa considerando las diferencias angulares en la curvatura de los puntos del mismo. El entrenamiento de cada modelo se realiza tanto con la descripción normal de los contornos como con la representación de la rotación de los mismos, para garantizar una mayor estabilidad en los parámetros estimados. Se desarrolla un proceso de validación cruzada de 5x1 para estimación del error. Se obtienen las medidas de sensibilidad, precisión y especificidad de la clasificación. Los mejores resultados en cuanto a sensibilidad se obtienen al clasificar eritrocitos pertenecientes a dos clases: normales (96 por ciento) y elongados (99 por ciento). Al considerar además una clase de eritrocitos con otras deformaciones los mejores resultados se obtienen realizando el entrenamiento de los modelos con la rotación de todos los contornos, que alcanzó sensibilidades de normales (94 por ciento), elongados (82 por ciento) y con otras deformaciones (76 por ciento)(AU)

A study of the performance of Hidden Markov Models (HMM) in morphologic supervised classification of erythrocytes in peripheral blood smears of patients with sickle cell disease is realized. Contours are represented in original way considering the angular differences in the curvature of the points of the same. The training of every model comes true with the normal description of the contours and with the representation of the rotation of the same, in order to guarantee a bigger stability in the esteemed parameters. A process of validation crossed of 5x1 for estimate of the error is developed. The measures of sensibility, precision and specificity of classification are obtained. The best results obtain when classifying erythrocytes in two classes, with sensibility values in normal of 96 percent and elongated 99 percent. In the classification of erythrocytes considering the class of other deformations better results obtain accomplishing the training of the models with the rotation of all the contours, that it attained sensibilities of normal (94 percent), elongated (82 percent) and with other deformations (76 percent)(AU)

A Review of Three Different Studies on Hidden Markov Models for Epigenetic Problems: A Computational Perspective

Recent technical advances, such as chromatin immunoprecipitation combined with DNA microarrays (ChIp-chip) and chromatin immunoprecipitation-sequencing (ChIP-seq), have generated large quantities of high-throughput data. Considering that epigenomic datasets are arranged over chromosomes, their analysis must account for spatial or temporal characteristics. In that sense, simple clustering or classification methodologies are inadequate for the analysis of multi-track ChIP-chip or ChIP-seq data. Approaches that are based on hidden Markov models (HMMs) can integrate dependencies between directly adjacent measurements in the genome. Here, we review three HMM-based studies that have contributed to epigenetic research, from a computational perspective. We also give a brief tutorial on HMM modelling-targeted at bioinformaticians who are new to the field.