Jari Björne

Background: The Critical Assessment of Functional Annotation (CAFA) is a community effort held to understand the field of computational protein function prediction. Every three years, since 2010, the organizers initiate an experiment to collect function predictions on a large set of proteins and then evaluate the performance of predicting methods on a subset of proteins that have accumulated experimental annotations between the submission deadline and the evaluation time. CAFA provides an independent and rigorous assessment of the current state of the art, thus leveling the playing field, highlighting successes, revealing bottlenecks, and offering a forum for the exchange of ideas in protein science. Here, we report the results of the fourth CAFA experiment (CAFA4). Results: CAFA4 featured the participation of 148 methods from 70 research groups on a total of 46,205 unique proteins over a 5-year annotation accumulation phase, the longest in any CAFA. In a comparison across CAFA2-CAFA4 methods, the prediction of Gene Ontology (GO) terms has clearly improved across all three GO aspects and traditional evaluation settings. While not achieving the first rank, several CAFA2 and CAFA3 methods featured in the top ten methods in many evaluations, suggesting that earlier methods still hold relevance. The performance is weaker in the newly introduced “partial knowledge” evaluation category (proteins with experimental annotations before submission deadline that gained additional annotations in the same GO aspect during the annotation accumulation phase), highlighting the need for a new class of methods. The rankings of the methods were stable over the years in traditional evaluation settings, but less so in the new partial knowledge evaluation. Overall, the field continues to progress with some influx of new participants. Sustained efforts will be necessary to substantially advance it.

Background: Recent advances in representation learning have enabled large strides in natural language understanding; However, verbal reasoning remains a challenge for state-of-the-art systems. External sources of structured, expert-curated verb-related knowledge have been shown to boost model performance in different Natural Language Processing (NLP) tasks where accurate handling of verb meaning and behaviour is critical. The costliness and time required for manual lexicon construction has been a major obstacle to porting the benefits of such resources to NLP in specialised domains, such as biomedicine. To address this issue, we combine a neural classification method with expert annotation to create BioVerbNet. This new resource comprises 693 verbs assigned to 22 top-level and 117 fine-grained semantic-syntactic verb classes. We make this resource available complete with semantic roles and VerbNet-style syntactic frames.Results: We demonstrate the utility of the new resource in boosting model performance in document- and sentence-level classification in biomedicine. We apply an established retrofitting method to harness the verb class membership knowledge from BioVerbNet and transform a pretrained word embedding space by pulling together verbs belonging to the same semantic-syntactic class. The BioVerbNet knowledge-aware embeddings surpass the non-specialised baseline by a significant margin on both tasks.Conclusion: This work introduces the first large, annotated semantic-syntactic classification of biomedical verbs, providing a detailed account of the annotation process, the key differences in verb behaviour between the general and biomedical domain, and the design choices made to accurately capture the meaning and properties of verbs used in biomedical texts. The demonstrated benefits of leveraging BioVerbNet in text classification suggest the resource could help systems better tackle challenging NLP tasks in biomedicine.

Over the past decade, the demand for automated protein function prediction has increased due to the volume of newly sequenced proteins. In this paper, we address the function prediction task by developing an ensemble system automatically assigning Gene Ontology (GO) terms to the given input protein sequence. We develop an ensemble system which combines the GO predictions made by random forest (RF) and neural network (NN) classifiers. Both RF and NN models rely on features derived from BLAST sequence alignments, taxonomy and protein signature analysis tools. In addition, we report on experiments with a NN model that directly analyzes the amino acid sequence as its sole input, using a convolutional layer. The Swiss-Prot database is used as the training and evaluation data. In the CAFA3 evaluation, which relies on experimental verification of the functional predictions, our submitted ensemble model demonstrates competitive performance ranking among top-10 best-performing systems out of over 100 submitted systems. In this paper, we evaluate and further improve the CAFA3-submitted system. Our machine learning models together with the data pre-processing and feature generation tools are publicly available as an open source software at https://github.com/TurkuNLP/CAFA3.

Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion: We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Over the past decade, the demand for automated protein function prediction has increased due to the volume of newly sequenced proteins. In this paper, we address the function prediction task by developing an ensemble system automatically assigning Gene Ontology (GO) terms to the given input protein sequence. We develop an ensemble system which combines the GO predictions made by random forest (RF) and neural network (NN) classifiers. Both RF and NN models rely on features derived from BLAST sequence alignments, taxonomy and protein signature analysis tools. In addition, we report on experiments with a NN model that directly analyzes the amino acid sequence as its sole input, using a convolutional layer. The Swiss-Prot database is used as the training and evaluation data. In the CAFA3 evaluation, which relies on experimental verification of the functional predictions, our submitted ensemble model demonstrates competitive performance ranking among top-10 best-performing systems out of over 100 submitted systems. In this paper, we evaluate and further improve the CAFA3-submitted system. Our machine learning models together with the data pre-processing and feature generation tools are publicly available as an open source software at https://github.com/TurkuNLP/CAFA3 Author summary: Understanding the role and function of proteins in biological processes is fundamental for new biological discoveries. Whereas modern sequencing methods have led to a rapid growth of protein databases, the function of these sequences is often unknown and expensive to determine experimentally. This has spurred a lot of interest in predictive modelling of protein functions. We develop a machine learning system for annotating protein sequences with functional definitions selected from a vast set of predefined functions. The approach is based on a combination of neural network and random forest classifiers with features covering structural and taxonomic properties and sequence similarity. The system is thoroughly evaluated on a large set of manually curated functional annotations and shows competitive performance in comparison to other suggested approaches. We also analyze the predictions for different functional annotation and taxonomy categories and measure the importance of different features for the task. This analysis reveals that the system is particularly efficient for bacterial protein sequences.

Biomedical researchers regularly discover new interactions between chemical compounds/drugs and genes/proteins, and report them in research literature. Having knowledge about these interactions is crucially important in many research areas such as precision medicine and drug discovery. The BioCreative VI Task 5 (CHEMPROT) challenge promotes the development and evaluation of computer systems that can automatically recognize and extract statements of such interactions from biomedical literature. We participated in this challenge with a Support Vector Machine (SVM) system and a deep learning-based system (ST-ANN), and achieved an F-score of 60.99 for the task. After the shared task, we have significantly improved the performance of the ST-ANN system. Additionally, we have developed a new deep learning-based system (I-ANN) that considerably outperforms the ST-ANN system. Both ST-ANN and I-ANN systems are centered around training an ensemble of artificial neural networks and utilizing different bidirectional Long Short-Term Memory (LSTM) chains for representing the shortest dependency path and/or the full sentence. By combining the predictions of the SVM and the I-ANN systems, we achieved an F-score of 63.10 for the task, improving our previous F-score by 2.11 percentage points. Our systems are fully open-source and publicly available. We highlight that the systems we present in this study are not applicable only to the BioCreative VI Task 5, but can be effortlessly re-trained to extract any types of relations of interest, with no modifications of the source code required, if a manually annotated corpus is provided as training data in a specific file format.