Identifying chemical entities on literature:a machine learning approach using dictionaries as domain knowledge

Tese de doutoramento, Informática (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2013The volume of life science publications, and therefore the underlying biomedical knowledge, are growing at a fast pace. However the manual literature analysis is a slow and painful task. Hence, text mining systems have been developed to automatically locate the relevant information contained in the literature. An essential step in text mining is named entitiy recognition, but the inherent complexity of biomedical entities, such as chemical compounds, makes it difficult to obtain good performances in this task. This thesis proposes methods capable to improve the current performance of chemical entity recognition from text. Hereby a case based method for recognizing chemical entities is proposed and the obtained evaluation results outperform the most widely used methods, based in dictionaries. A lexical similarity based chemical entity resolution method was also developed and allows an efficient mapping of the recognized entities to the ChEBI database. To improve the chemical entity identification results we developed a validation method that exploits the semantic relationships in ChEBI to measure the similarity between the entities found in the text, in order to discriminate between the correctly identified entities that can be validated and identification errors that should be discarded. A machine learning method for entity recognition error is also proposed, which can efectively find recognition errors in rule based systems. The methods were integrated in a system capable of recognizing chemical entities in texts, map them to the ChEBI database, and provide evidence of validation or recognition error for the recognized entities.O volume de publicações científicas nas ciências da vida está a aumentar a um ritmo crescente. Contudo a análise manual da literatura é um processo árduo e moroso, pelo que têm sido desenvolvidos sistemas de prospecção de texto para identificar automaticamente a informação relevante contida na literatura. Um passo essencial em prospecção de texto é a identificação de entidades nomeadas, mas a complexidade inerente às entidades biomédicas, como é o caso dos compostos químicos, torna difícil obter bons desempenhos nesta tarefa. Esta tese propõe métodos para melhorar o desempenho actual do processo de reconhecimento de entidades químicas em texto. Para tal propõe-se um método para reconhecimento de entidades químicas baseado em aprendizagem automática, que obteve resultados superiores aos métodos baseados em dicionários utilizados actualmente. Desenvolveu-se ainda um método baseado em semelhança lexical que realiza o mapeamento de entidades para a ontologia ChEBI. Para melhorar os resultados de identificação de entidades químicas desenvolveu-se um método de validação que explora as relações semânticas do ChEBI para medir a semelhança entre as entidades encontradas no texto, de forma a discriminar as entidades correctamente identificadas dos erros de identificação. Um método de filtragem de erros baseado em aprendizagem automática é também proposto, e foi testado num sistema baseado em regras. Estes métodos foram integrados num sistema capaz de reconhecer as entidades químicas em texto, mapear para o ChEBI, e fornecer evidência para validação ou detecção de erros das entidades reconhecidas.Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/36015/2007

InterPro in 2022.

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. Here, we report recent developments with InterPro (version 90.0) and its associated software, including updates to data content and to the website. These developments extend and enrich the information provided by InterPro, and provide a more user friendly access to the data. Additionally, we have worked on adding Pfam website features to the InterPro website, as the Pfam website will be retired in late 2022. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB. Moreover, we report the development of a card game as a method of engaging the non-scientific community. Finally, we discuss the benefits and challenges brought by the use of artificial intelligence for protein structure prediction

One-step generation of conditional and reversible gene knockouts

Loss-of-function studies are key for investigating gene function, and CRISPR technology has made genome editing widely accessible in model organisms and cells. However, conditional gene inactivation in diploid cells is still difficult to achieve. Here, we present CRISPR-FLIP, a strategy that provides an efficient, rapid and scalable method for biallelic conditional gene knockouts in diploid or aneuploid cells, such as pluripotent stem cells, 3D organoids and cell lines, by co-delivery of CRISPR-Cas9 and a universal conditional intronic cassette.A.A.-R. and K.T. are supported by the Medical Research Council, A.M. is supported by Wntsapp, Marie Curie ITN. J.F. and J.C.R.S. are supported by the Wellcome Trust. W.C.S. received core grant support from the Wellcome Trust to the Wellcome Trust Sanger Institute. B.-K.K. and R.C.M. are supported by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (101241/Z/13/Z) and receive a core support grant from the Wellcome Trust and MRC to the WT–MRC Cambridge Stem Cell Institute

GENCODE reference annotation for the human and mouse genomes

The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.National Human Genome Research Institute of the National Institutes of Healt

Enhancement of chemical entity identification in text using semantic similarity validation.

With the amount of chemical data being produced and reported in the literature growing at a fast pace, it is increasingly important to efficiently retrieve this information. To tackle this issue text mining tools have been applied, but despite their good performance they still provide many errors that we believe can be filtered by using semantic similarity. Thus, this paper proposes a novel method that receives the results of chemical entity identification systems, such as Whatizit, and exploits the semantic relationships in ChEBI to measure the similarity between the entities found in the text. The method assigns a single validation score to each entity based on its similarities with the other entities also identified in the text. Then, by using a given threshold, the method selects a set of validated entities and a set of outlier entities. We evaluated our method using the results of two state-of-the-art chemical entity identification tools, three semantic similarity measures and two text window sizes. The method was able to increase precision without filtering a significant number of correctly identified entities. This means that the method can effectively discriminate the correctly identified chemical entities, while discarding a significant number of identification errors. For example, selecting a validation set with 75% of all identified entities, we were able to increase the precision by 28% for one of the chemical entity identification tools (Whatizit), maintaining in that subset 97% the correctly identified entities. Our method can be directly used as an add-on by any state-of-the-art entity identification tool that provides mappings to a database, in order to improve their results. The proposed method is included in a freely accessible web tool at www.lasige.di.fc.ul.pt/webtools/ice/

Validation of Whatizit annotation results.

<p>Shows the variation in precision and recall with the validation score threshold, using the Resnik measure with a document as text window. Straight dots represent the expected behavior of a random validation system.</p

Comparison of the validation scores.

<p>Boxplot of the validation score obtained for the manual annotations in the gold standard, and the automatic annotations provided by the dictionary-based method and the CRF-based method.</p

Validation of CRF-based annotation results.

<p>Shows the variation in precision and recall with the validation score threshold, using the Resnik measure with a document as text window. Straight dots represent the expected behavior of a random validation system.</p