Development of a deep learning-based computational framework for the classification of protein sequences

Dissertação de mestrado em BioinformaticsProteins are one of the more important biological structures in living organisms, since they perform multiple biological functions. Each protein has different characteristics and properties, which can be employed in many industries, such as industrial biotechnology, clinical applications, among others, demonstrating a positive impact. Modern high-throughput methods allow protein sequencing, which provides the protein sequence data. Machine learning methodologies are applied to characterize proteins using information of the protein sequence. However, a major problem associated with this method is how to properly encode the protein sequences without losing the biological relationship between the amino acid residues. The transformation of the protein sequence into a numeric representation is done by encoder methods. In this sense, the main objective of this project is to study different encoders and identify the methods which yield the best biological representation of the protein sequences, when used in machine learning (ML) models to predict different labels related to their function. The methods were analyzed in two study cases. The first is related to enzymes, since they are a well-established case in the literature. The second used transporter sequences, a lesser studied case in the literature. In both cases, the data was collected from the curated database Swiss-Prot. The encoders that were tested include: calculated protein descriptors; matrix substitution methods; position-specific scoring matrices; and encoding by pre-trained transformer methods. The use of state-of-the-art pretrained transformers to encode protein sequences proved to be a good biological representation for subsequent application in state-of-the-art ML methods. Namely, the ESM-1b transformer achieved a Mathews correlation coefficient above 0.9 for any multiclassification task of the transporter classification system.As proteínas são estruturas biológicas importantes dos organismos vivos, uma vez que estas desempenham múltiplas funções biológicas. Cada proteína tem características e propriedades diferentes, que podem ser aplicadas em diversas indústrias, tais como a biotecnologia industrial, aplicações clínicas, entre outras, demonstrando um impacto positivo. Os métodos modernos de alto rendimento permitem a sequenciação de proteínas, fornecendo dados da sequência proteica. Metodologias de aprendizagem de máquinas tem sido aplicada para caracterizar as proteínas utilizando informação da sua sequência. Um problema associado a este método e como representar adequadamente as sequências proteicas sem perder a relação biológica entre os resíduos de aminoácidos. A transformação da sequência de proteínas numa representação numérica é feita por codificadores. Neste sentido, o principal objetivo deste projeto é estudar diferentes codificadores e identificar os métodos que produzem a melhor representação biológica das sequências proteicas, quando utilizados em modelos de aprendizagem mecânica para prever a classificação associada à sua função a sua função. Os métodos foram analisados em dois casos de estudo. O primeiro caso foi baseado em enzimas, uma vez que são um caso bem estabelecido na literatura. O segundo, na utilização de proteínas de transportadores, um caso menos estudado na literatura. Em ambos os casos, os dados foram recolhidos a partir da base de dados curada Swiss-Prot. Os codificadores testados incluem: descritores de proteínas calculados; métodos de substituição por matrizes; matrizes de pontuação específicas da posição; e codificação por modelos de transformadores pré-treinados. A utilização de transformadores de última geração para codificar sequências de proteínas demonstrou ser uma boa representação biológica para aplicação subsequente em métodos ML de última geração. Nomeadamente, o transformador ESM-1b atingiu um coeficiente de correlação de Matthews acima de 0,9 para multiclassificação do sistema de classificação de proteínas transportadoras

Nationwide access to endovascular treatment for acute ischemic stroke in portugal

Publisher Copyright: Copyright Ordem dos M dicos 2021.Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. Discussion: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions. Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitalspublishersversionpublishe

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Intoxicações por plantas em ruminantes e equídeos na região central de Rondônia Plant poisonings in ruminants and equidae in central region of Rondônia state, Northern Brazil

Foi realizado um levantamento em 12 municípios da região central de Rondônia sobre a presença de plantas tóxicas e ocorrência de surtos de intoxicação em ruminantes e equídeos. O trabalho foi desenvolvido mediante a utilização de um questionário aplicado a médicos veterinários, agrônomos, zootecnistas e produtores rurais, com o objetivo de identificar as principais plantas tóxicas que ocorrem na região. Trinta e quatro entrevistados relataram casos de intoxicação por uma ou mais plantas comprovadamente tóxicas como: Palicourea marcgravii (12 surtos), Palicourea grandiflora e Enterolobium contortisiliquum (sete surtos cada) e Palicourea juruana, Brachiaria radicans, Brachiaria brizantha e Manihot esculenta (dois surtos cada). Em ovinos, foram relatados dois surtos de fotossensiblização por Brachiaria decumbens e um surto de mortalidade por Palicourea grandiflora. Dos 34 surtos relatados em bovinos pelos entrevistados, 374 (8,9%) animais foram afetados e 311 (7,4%) morreram, de um total de 4.192 de ambos os sexos sob risco. De um total de 250 ovinos sob risco, três surtos de intoxicação por plantas foram relatados e afetaram 28 animais, dos quais 20 morreram. Amorimia sp., previamente desconhecida como tóxica, foi identificada como causa de morte súbita em 32% das propriedades. Quinze surtos de cólica em equídeos que pastavam cultivares de Panicum maximum ('Massai', 'Tanzânia' e 'Mombaça') durante o período das chuvas foram, também, observados. Os resultados do presente trabalho demonstram a importância significativa das intoxicações por plantas como causa de perdas econômicas para a pecuária da região central do Estado de Rondônia. Com a realização deste trabalho, o número de plantas tóxicas para ruminantes com a confirmação de ocorrência de surtos com mortalidade na região passou de um para nove, o que confirma que um trabalho sistemático de investigação é necessário para o conhecimento da importância das intoxicações por plantas na região Norte do Brasil.<br>A survey about the presence of toxic plants and the occurrence of outbreaks of poisoning in ruminants and equidae was performed in 12 municipalities of the central region of the state of Rondônia. Ninety eight persons were interviewed, including farmers, veterinary practitioners, agronomists, and agrarian technicians. Thirty four farmers reported poisoning by toxic plants, including poisoning by Palicourea marcgravii (12 outbreaks), Palicourea grandiflora and Enterolobium contortisiliquum (seven outbreaks each), and Palicourea juruana, Brachiaria radicans, Brachiaria brizantha, and Manihot esculenta (two outbreaks each). In sheep, farmers reported two outbreaks of photosensitization caused by Brachiaria decumbens and one outbreak of sudden death caused by Palicourea grandiflora. In the 34 outbreaks, 374 (8,9%) bovines were affected and 311 (7.4%) died, from a total of 4.192 cattle exposed. In the three outbreaks in sheep, 28 animals were affected and 20 died out of 250 exposed. Amorimia sp., previously misidentified as Mascagnia sepium, a previously unreported toxic plant, was identified as a cause of sudden death in sheep and cattle in 32% of the farms. Fifteen outbreaks of colic in horses grazing Panicum maximum (cultivars 'Massai', 'Tanzânia', and 'Mombaça') during the rainy season were also reported. It is concluded that poisoning by toxic plants is an important cause of economic losses in livestock in the region studied. With the results of this research the number of known toxic plant for ruminants in central region of Rondônia increased from one to nine, indicating that more research is necessary for the knowledge of poisonous plants for livestock in the Brazilian Amazonic region

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

Núcleos de Ensino da Unesp: artigos 2008

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq