Computational toolbox towards evolutionary domain mapping of membrane proteins

Curs 2012-2013Membrane proteins account for about 20% to 30% of all proteins encoded in a typical genome. They play central roles in multiple cellular processes mediating the interaction of the cell with its surrounding. Over 60% of all drug targets contain a membrane domain. The experimental difficulties of obtaining a crystal structural severely limits our ability or understanding of membrane protein function. Computational evolutionary studies of proteins are crucial for the prediction of 3D structures. In this project, we construct a tool able to quantify the evolutionary positive selective pressure on each residue of membrane proteins through maximum likelihood phylogeny reconstruction. The conservation plot combined with a structural homology model is also a potent tool to predict those residues that have essentials roles in the structure and function of a membrane protein and can be very useful in the design of validation experiments.Director/a: Mireia Olivella i Alex Peràlvare

1936. "Hogueras en la noche" i les mines de Fígols

El 23 de febrero de 1936 s'estrenava a Barcelona la pel·lícula "Hogueras en la noche", un llargmetratge filmat als estudis Orphea de la ciutat comtal, i amb exteriors rodats a la mateixa ciutat de Barcelona i al complex miner de Fígols- Les mine

Characterising the source of errors for metagenomic taxonomic classification

Characterising microbial communities enables a better understanding of their complexity and the contribution to the environment. Metagenomics has been a rapidly expanding field since the revolution of next generation sequencing began, and it has a wide range of application including for medicine, agriculture, forensics, archaeology and even domestic use [Sarkar et al., 2021, Holman et al., 2017, Khodakova et al.,2014, Santiago-Rodriguez et al., 2017, Vilanova et al., 2015]. Sequencing amplicon data, such as 16S rRNA, is now commonly used to characterise the microbiome in a variety of biological samples. However, their correct taxonomic identification still remains a challenge, and often short reads are identified, correctly or not, at several ranks of the taxonomic tree other than species or subspecies level. Every metagenomic study is designed for specific needs, and it is often complicated to find a suitable bioinformatics pipeline and reference database. There is currently a lack of systematic benchmarking of in-house methods for metagenomics. The work presented in this thesis aims to establish an approach for the in silico validation of 16S rRNA metagenomic data. A method to generate realistic in silico metagenome data that resembles project-specific sequencing data is presented, including a new process to generate synthetic negative controls for amplicon data, which can be employed regularly to assess the appropriateness and optimisation of methods for specific metagenomic projects. To aid the benchmarking process, new metrics have been defined based on a measure of taxonomic distance. A k-mer based method with the lowest common ancestor approach was selected to investigate a range of factors that influence meta-taxonomic classification success. It includes the comparison of database quality filtered at various levels, and as well as a comparison of different taxonomic annotation methodologies. The experimental findings reveal the importance of having highly curated taxonomic annotations of the genetic sequences in the database, and that a missing fraction of the tree of life can lead to misclassification of any related or unrelated organisms. In some cases, it is shown that longer reads can help to improve assignment, with mutations and sequencing errors having a relatively low negative impact. The marker gene 16S rRNA has well-defined conserved and variable regions, which help to distinguish species. Therefore, these regions were studied and also recalculated using information theory, to investigate which parts of the sequence are discriminative for metagenomic taxonomic identification. In addition, linguistics methods, Term Frequency — Inverse Document Frequency (TF-IDF) coupled with multinomial naive Bayes, is shown to provide understanding of genetic signatures and is applied to generate a new method to classify taxonomically metagenomics short reads. Biological samples were taken from cattle respiratory tract, DNA was extracted and sequenced to provide metagenomic data. Two sets of experiments were carried out, (i) to compare sampling and extraction methods and (ii) to characterise the microbial community observed in young cattle in the different lung lobes and nose. The data reveal that the composition of the microbial community observed is highly dependent on the sampling method

GRAIMATTER Green Paper:Recommendations for disclosure control of trained Machine Learning (ML) models from Trusted Research Environments (TREs)

TREs are widely, and increasingly used to support statistical analysis of sensitive data across a range of sectors (e.g., health, police, tax and education) as they enable secure and transparent research whilst protecting data confidentiality.There is an increasing desire from academia and industry to train AI models in TREs. The field of AI is developing quickly with applications including spotting human errors, streamlining processes, task automation and decision support. These complex AI models require more information to describe and reproduce, increasing the possibility that sensitive personal data can be inferred from such descriptions. TREs do not have mature processes and controls against these risks. This is a complex topic, and it is unreasonable to expect all TREs to be aware of all risks or that TRE researchers have addressed these risks in AI-specific training.GRAIMATTER has developed a draft set of usable recommendations for TREs to guard against the additional risks when disclosing trained AI models from TREs. The development of these recommendations has been funded by the GRAIMATTER UKRI DARE UK sprint research project. This version of our recommendations was published at the end of the project in September 2022. During the course of the project, we have identified many areas for future investigations to expand and test these recommendations in practice. Therefore, we expect that this document will evolve over time. The GRAIMATTER DARE UK sprint project has also developed a minimal viable product (MVP) as a suite of attack simulations that can be applied by TREs and can be accessed here (https://github.com/AI-SDC/AI-SDC).If you would like to provide feedback or would like to learn more, please contact Smarti Reel ([email protected]) and Emily Jefferson ([email protected]).The summary of our recommendations for a general public audience can be found at DOI: 10.5281/zenodo.708951

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients

Guix

Resumen tomado de la publicaciónEl Museo de las Minas de Cercs es un museo de técnica y de historia dedicado al carbón. Se pretende que sea un centro de interpretación para dar a conocer este combustible y el entorno geológico, paisajístico, económico y humano del Alt Berguedà..CataluñaUniversitat de Barcelona. Biblioteca de Ciències de l'Educació; Passeig de la Vall d'hebron, 171; 08035 Barcelona; +34934021035; +34934021034;ES