Artificial intelligence-driven prediction of COVID-19-related hospitalization and death: a systematic review

AimTo perform a systematic review on the use of Artificial Intelligence (AI) techniques for predicting COVID-19 hospitalization and mortality using primary and secondary data sources.Study eligibility criteriaCohort, clinical trials, meta-analyses, and observational studies investigating COVID-19 hospitalization or mortality using artificial intelligence techniques were eligible. Articles without a full text available in the English language were excluded.Data sourcesArticles recorded in Ovid MEDLINE from 01/01/2019 to 22/08/2022 were screened.Data extractionWe extracted information on data sources, AI models, and epidemiological aspects of retrieved studies.Bias assessmentA bias assessment of AI models was done using PROBAST.ParticipantsPatients tested positive for COVID-19.ResultsWe included 39 studies related to AI-based prediction of hospitalization and death related to COVID-19. The articles were published in the period 2019-2022, and mostly used Random Forest as the model with the best performance. AI models were trained using cohorts of individuals sampled from populations of European and non-European countries, mostly with cohort sample size <5,000. Data collection generally included information on demographics, clinical records, laboratory results, and pharmacological treatments (i.e., high-dimensional datasets). In most studies, the models were internally validated with cross-validation, but the majority of studies lacked external validation and calibration. Covariates were not prioritized using ensemble approaches in most of the studies, however, models still showed moderately good performances with Area under the Receiver operating characteristic Curve (AUC) values >0.7. According to the assessment with PROBAST, all models had a high risk of bias and/or concern regarding applicability.ConclusionsA broad range of AI techniques have been used to predict COVID-19 hospitalization and mortality. The studies reported good prediction performance of AI models, however, high risk of bias and/or concern regarding applicability were detected

The Genomic HyperBrowser: an analysis web server for genome-scale data

The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, researchers are faced with the challenge of how to best analyze and interpret their genome-scale datasets. A powerful way of representing genome-scale data is as feature-specific coordinates relative to reference genome assemblies, i.e. as genomic tracks. The Genomic HyperBrowser (http://hyperbrowser.uio.no) is an open-ended web server for the analysis of genomic track data. Through the provision of several highly customizable components for processing and statistical analysis of genomic tracks, the HyperBrowser opens for a range of genomic investigations, related to, e.g., gene regulation, disease association or epigenetic modifications of the genome

The Genomic HyperBrowser: an analysis web server for genome-scale data

The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, researchers are faced with the challenge of how to best analyze and interpret their genome-scale datasets. A powerful way of representing genome-scale data is as feature-specific coordinates relative to reference genome assemblies, i.e. as genomic tracks. The Genomic HyperBrowser (http://hyperbrowser.uio.no) is an open-ended web server for the analysis of genomic track data. Through the provision of several highly customizable components for processing and statistical analysis of genomic tracks, the HyperBrowser opens for a range of genomic investigations, related to, e.g., gene regulation, disease association or epigenetic modifications of the genome.publishedVersio

GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome

Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.This work was supported by the Research Council of Norway (under grant agreements 221580, 218241, and 231217/F20), by the Norwegian Cancer Society (under grant agreements 71220’PR-2006-0433 and 3485238-2013), and by the South-Eastern Norway Regional Health Authority (under grant agreement 2014041).Peer Reviewe

Potentials and limitations of motif-based binding site prediction in DNA

As the full genomic DNA sequence is now available for several organisms, a major next challenge is determining the function of DNA elements. This task is often referred to as functional genomics. An important part of functional genomics is gene regulation, and particularly the binding of specific proteins called Transcription Factors (TFs) to DNA. This TF binding regulates the production of mRNA, and thereby eventually proteins, from genes. As experimental determination of TF binding sites in DNA is a very laborious process, there is great interest in computational prediction methods. The basic idea behind computational binding site prediction is to use motifs (sequence patterns) to capture sequence similarity between separate binding sites for a given TF. Based on a set of known binding site examples, the sequence similarity can be exploited for prediction of additional binding sites for a given TF. As motifs representing TF binding sites should occur more frequently than expected by chance alone in co-regulated DNA sequences, computational methods can even be used to discover novel TF binding site motifs and associated binding sites using only un-annotated target DNA sequences as input. The focus of this thesis is on the computational prediction of TF binding sites, and specifically on understanding the current limitations and potential for improvement of binding site prediction. Two of the papers in the thesis relate to the assessment of computational predictions. The data sets used in a recent benchmark of prediction methods is analyzed in relation to three commonly used motif models, showing some fundamental performance limitations that should be attributed either to the motif models or to the benchmark data sets themselves. A first broad benchmark of methods predicting higher-order organization of TF binding sites is also part of this thesis. The benchmark showed some differences in prediction accuracy between methods, and more generally that a moderate level of prediction accuracy can be expected in the considered scenario. Two novel motif discovery methods are also presented in the thesis. Both of the methods consider the problem of predicting higher-order organization of binding sites, given motifs representing binding of individual TFs as input. One method takes a Bayesian probabilistic approach to binding site modeling, while the other method uses a discrete approach. Both methods use highly expressive models and show good quantitative performance in relation to existing methods. Each method also introduces some additional elements that may bring qualitative advantages. A third and final direction of research in this thesis concerns the extended process of motif discovery in DNA. Topics considered include how data is compiled before binding site prediction is performed, how prediction results can be interpreted in a multiple-testing scenario, and how prediction can be accelerated by the use of parallel hardware

CompAIRR: ultra-fast comparison of adaptive immune receptor repertoires by exact and approximate sequence matching

Abstract Motivation Adaptive immune receptor (AIR) repertoires (AIRRs) record past immune encounters with exquisite specificity. Therefore, identifying identical or similar AIR sequences across individuals is a key step in AIRR analysis for revealing convergent immune response patterns that may be exploited for diagnostics and therapy. Existing methods for quantifying AIRR overlap scale poorly with increasing dataset numbers and sizes. To address this limitation, we developed CompAIRR, which enables ultra-fast computation of AIRR overlap, based on either exact or approximate sequence matching. Results CompAIRR improves computational speed 1000-fold relative to the state of the art and uses only one-third of the memory: on the same machine, the exact pairwise AIRR overlap of 104 AIRRs with 105 sequences is found in ∼17 min, while the fastest alternative tool requires 10 days. CompAIRR has been integrated with the machine learning ecosystem immuneML to speed up commonly used AIRR-based machine learning applications. Availability and implementation CompAIRR code and documentation are available at https://github.com/uio-bmi/compairr. Docker images are available at https://hub.docker.com/r/torognes/compairr. The code to replicate the synthetic datasets, scripts for benchmarking and creating figures, and all raw data underlying the figures are available at https://github.com/uio-bmi/compairr-benchmarking. Supplementary information Supplementary data are available at Bioinformatics online

ClusTrack: Feature extraction and similarity measures for clustering of genome-wide data sets

Clustering is a popular technique for explorative analysis of data, as it can reveal subgroupings and similarities between data in an unsupervised manner. While clustering is routinely applied to gene expression data, there is a lack of appropriate general methodology for clustering of sequence-level genomic and epigenomic data, e.g. ChIP-based data. We here introduce a general methodology for clustering data sets of coordinates relative to a genome assembly, i.e. genomic tracks. By defining appropriate feature extraction approaches and similarity measures, we allow biologically meaningful clustering to be performed for genomic tracks using standard clustering algorithms. An implementation of the methodology is provided through a tool, ClusTrack, which allows fine-tuned clustering analyses to be specified through a web-based interface. We apply our methods to the clustering of occupancy of the H3K4me1 histone modification in samples from a range of different cell types. The majority of samples form meaningful subclusters, confirming that the definitions of features and similarity capture biological, rather than technical, variation between the genomic tracks. Input data and results are available, and can be reproduced, through a Galaxy Pages document at http://hyperbrowser.uio.no/hb/u/hb-superuser/p/clustrack. The clustering functionality is available as a Galaxy tool, under the menu option "Specialized analyzis of tracks", and the submenu option "Cluster tracks based on genome level similarity", at the Genomic HyperBrowser server: http://hyperbrowser.uio.no/hb/