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Abstract Current research in nephrology is increasingly focused on elucidating the complexity inherent in tightly interwoven molecular systems and their correlation with pathology and related therapeutics, including dialysis and renal transplantation. Rapid advances in the omics sciences, medical device sensorization, and networked digital medical devices have made such research increasingly data centered. Data-centric science requires the support of computationally powerful and sophisticated tools able to handle the overflow of novel biomarkers and therapeutic targets. This is a context in which artificial intelligence (AI) and, more specifically, machine learning (ML) can provide a clear analytical advantage, given the rapid advances in their ability to harness multimodal data, from genomic information to signal, image and even heterogeneous electronic health records (EHR). However, paradoxically, only a small fraction of ML-based medical decision support systems undergo validation and demonstrate clinical usefulness. To effectively translate all this new knowledge into clinical practice, the development of clinically compliant support systems based on interpretable and explainable ML-based methods and clear analytical strategies for personalized medicine are imperative. Intelligent nephrology, that is, the design and development of AI-based strategies for a data-centric approach to nephrology, is just taking its first steps and is by no means yet close to its coming of age. These first steps are not even homogeneously taken, as a digital divide in access to technology has become evident between developed and developing countries, also affecting underrepresented minorities. With all this in mind, this editorial aim to provide a selective overview of the current use of AI technologies in nephrology and heralds the “Artificial Intelligence in Nephrology” special issue launched by BMC Nephrology.

Abstract Purpose The analysis of absorption, distribution, metabolism, and excretion (ADME) molecular properties is of relevance to drug design, as they directly influence the drug’s effectiveness at its target location. This study concerns their prediction, using explainable Machine Learning (ML) models. The aim of the study is to find which molecular features are relevant to the prediction of the different ADME properties and measure their impact on the predictive model. Methods The relative relevance of individual features for ADME activity is gauged by estimating feature importance in ML models’ predictions. Feature importance is calculated using feature permutation and the individual impact of features is measured by SHAP additive explanations. Results The study reveals the relevance of specific molecular descriptors for each ADME property and quantifies their impact on the ADME property prediction. Conclusion The reported research illustrates how explainable ML models can provide detailed insights about the individual contributions of molecular features to the final prediction of an ADME property, as an effort to support experts in the process of drug candidate selection through a better understanding of the impact of molecular features.

Abstract G protein-coupled receptors (GPCRs) are a large superfamily of cell membrane proteins that play an important physiological role as transmitters of extracellular signals. Signal transmission through the cell membrane depends on conformational changes in the transmembrane region of the receptor, which makes the investigation of the dynamics in these regions particularly relevant. Molecular dynamics (MD) simulations provide a wealth of data about the structure, dynamics, and physiological function of biological macromolecules by modelling the interactions between their atomic constituents. In this study, a Recurrent and Convolutional Neural Network (RNN) model, namely Long Short-Term Memory (LSTM), is used to predict the dynamics of two GPCR states and three specific simulations of each one, through their activation path and focussing on specific receptor regions. Active and inactive states of the GPCRs are analysed in six scenarios involving APO, Full Agonist (BI 167107) and Partial Inverse Agonist (carazolol) of the receptor. Four Machine Learning models with increasing complexity in terms of neural network architecture are evaluated, and their results discussed. The best method achieves an overall RMSD lower than 0.139 Å and the transmembrane helices are the regions showing the minimum prediction errors and minimum relative movements of the protein.

Purpose: To evaluate the diagnostic accuracy of machine learning (ML) techniques applied to radiomic features extracted from OCT and OCT angiography (OCTA) images for diabetes mellitus (DM), diabetic retinopathy (DR), and referable DR (R-DR) diagnosis. Design: Cross-sectional analysis of a retinal image dataset from a previous prospective OCTA study (ClinicalTrials.gov NCT03422965). Participants: Patients with type 1 DM and controls included in the progenitor study. Methods: Radiomic features were extracted from fundus retinographies, OCT, and OCTA images in each study eye. Logistic regression, linear discriminant analysis, support vector classifier (SVC)-linear, SVC-radial basis function, and random forest models were created to evaluate their diagnostic accuracy for DM, DR, and R-DR diagnosis in all image types. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) mean and standard deviation for each ML model and each individual and combined image types. Results: A dataset of 726 eyes (439 individuals) were included. For DM diagnosis, the greatest AUC was observed for OCT (0.82, 0.03). For DR detection, the greatest AUC was observed for OCTA (0.77, 0.03), especially in the 3 × 3 mm superficial capillary plexus OCTA scan (0.76, 0.04). For R-DR diagnosis, the greatest AUC was observed for OCTA (0.87, 0.12) and the deep capillary plexus OCTA scan (0.86, 0.08). The addition of clinical variables (age, sex, etc.) improved most models AUC for DM, DR and R-DR diagnosis. The performance of the models was similar in unilateral and bilateral eyes image datasets. Conclusions: Radiomics extracted from OCT and OCTA images allow identification of patients with DM, DR, and R-DR using standard ML classifiers. OCT was the best test for DM diagnosis, OCTA for DR and R-DR diagnosis and the addition of clinical variables improved most models. This pioneer study demonstrates that radiomics-based ML techniques applied to OCT and OCTA images may be an option for DR screening in patients with type 1 DM. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Artificial intelligence (AI) generative models driven by the integration of AI and natural language processing technologies, such as OpenAI’s chatbot generative pre-trained transformer large language model (LLM), are receiving much public attention and have the potential to transform personalized medicine. Dialysis patients are highly dependent on technology and their treatment generates a challenging large volume of data that has to be analyzed for knowledge extraction. We argue that, by integrating the data acquired from hemodialysis treatments with the powerful conversational capabilities of LLMs, nephrologists could personalize treatments adapted to patients’ lifestyles and preferences. We also argue that this new conversational AI integrated with a personalized patient-computer interface will enhance patients’ engagement and self-care by providing them with a more personalized experience. However, generative AI models require continuous and accurate updates of data, and expert supervision and must address potential biases and limitations. Dialysis patients can also benefit from other new emerging technologies such as Digital Twins with which patients’ care can also be addressed from a personalized medicine perspective. In this paper, we will revise LLMs potential strengths in terms of their contribution to personalized medicine, and, in particular, their potential impact, and limitations in nephrology. Nephrologists’ collaboration with AI academia and companies, to develop algorithms and models that are more transparent, understandable, and trustworthy, will be crucial for the next generation of dialysis patients. The combination of technology, patient-specific data, and AI should contribute to create a more personalized and interactive dialysis process, improving patients’ quality of life.

Background: The 2019 Science for Dialysis Meeting at Bellvitge University Hospital was devoted to the challenges and opportunities posed by the use of data science to facilitate precision and personalized medicine in nephrology, and to describe new approaches and technologies. The meeting included separate sections for issues in data collection and data analysis. As part of data collection, we presented the institutional ARGOS e-health project, which provides a common model for the standardization of clinical practice. We also pay specific attention to the way in which randomized controlled trials offer data that may be critical to decision-making in the real world. The opportunities of open source software (OSS) for data science in clinical practice were also discussed. Summary: Precision medicine aims to provide the right treatment for the right patients at the right time and is deeply connected to data science. Dialysis patients are highly dependent on technology to live, and their treatment generates a huge volume of data that has to be analysed. Data science has emerged as a tool to provide an integrated approach to data collection, storage, cleaning, processing, analysis, and interpretation from potentially large volumes of information. This is meant to be a perspective article about data science based on the experience of the experts invited to the Science for Dialysis Meeting and provides an up-to-date perspective of the potential of data science in kidney disease and dialysis. Key messages: Healthcare is quickly becoming data-dependent, and data science is a discipline that holds the promise of contributing to the development of personalized medicine, although nephrology still lags behind in this process. The key idea is to ensure that data will guide medical decisions based on individual patient characteristics rather than on averages over a whole population usually based on randomized controlled trials that excluded kidney disease patients. Furthermore, there is increasing interest in obtaining data about the effectiveness of available treatments in current patient care based on pragmatic clinical trials. The use of data science in this context is becoming increasingly feasible in part thanks to the swift developments in OSS.

The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making in cardiology. The success of these tools is dependent on the understanding of the intrinsic processes being used during the conventional pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous steps to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with the two later tasks of interpretation and decision support, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes in cardiovascular imaging.

Abstract Background Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This challenge entails the daunting task of extracting usable knowledge from these data using algorithmic methods. In the medical context this may for instance realized through the design of medical decision support systems for diagnosis, prognosis and patient management. The intensive care unit (ICU), and by extension the whole area of critical care, is becoming one of the most data-driven clinical environments. Results The increasing availability of complex and heterogeneous data at the point of patient attention in critical care environments makes the development of fresh approaches to data analysis almost compulsory. Computational Intelligence (CI) and Machine Learning (ML) methods can provide such approaches and have already shown their usefulness in addressing problems in this context. The current study has a dual goal: it is first a review of the state-of-the-art on the use and application of such methods in the field of critical care. Such review is presented from the viewpoint of the different subfields of critical care, but also from the viewpoint of the different available ML and CI techniques. The second goal is presenting a collection of results that illustrate the breath of possibilities opened by ML and CI methods using a single problem, the investigation of septic shock at the ICU. Conclusion We have presented a structured state-of-the-art that illustrates the broad-ranging ways in which ML and CI methods can make a difference in problems affecting the manifold areas of critical care. The potential of ML and CI has been illustrated in detail through an example concerning the sepsis pathology. The new definitions of sepsis and the relevance of using the systemic inflammatory response syndrome (SIRS) in its diagnosis have been considered. Conditional independence models have been used to address this problem, showing that SIRS depends on both organ dysfunction measured through the Sequential Organ Failure (SOFA) score and the ICU outcome, thus concluding that SIRS should still be considered in the study of the pathophysiology of Sepsis. Current assessment of the risk of dead at the ICU lacks specificity. ML and CI techniques are shown to improve the assessment using both indicators already in place and other clinical variables that are routinely measured. Kernel methods in particular are shown to provide the best performance balance while being amenable to representation through graphical models, which increases their interpretability and, with it, their likelihood to be accepted in medical practice.

Abstract Background Biology is experiencing a gradual but fast transformation from a laboratory-centred science towards a data-centred one. As such, it requires robust data engineering and the use of quantitative data analysis methods as part of database curation. This paper focuses on G protein-coupled receptors, a large and heterogeneous super-family of cell membrane proteins of interest to biology in general. One of its families, Class C, is of particular interest to pharmacology and drug design. This family is quite heterogeneous on its own, and the discrimination of its several sub-families is a challenging problem. In the absence of known crystal structure, such discrimination must rely on their primary amino acid sequences. Methods We are interested not as much in achieving maximum sub-family discrimination accuracy using quantitative methods, but in exploring sequence misclassification behavior. Specifically, we are interested in isolating those sequences showing consistent misclassification, that is, sequences that are very often misclassified and almost always to the same wrong sub-family. Random forests are used for this analysis due to their ensemble nature, which makes them naturally suited to gauge the consistency of misclassification. This consistency is here defined through the voting scheme of their base tree classifiers. Results Detailed consistency results for the random forest ensemble classification were obtained for all receptors and for all data transformations of their unaligned primary sequences. Shortlists of the most consistently misclassified receptors for each subfamily and transformation, as well as an overall shortlist including those cases that were consistently misclassified across transformations, were obtained. The latter should be referred to experts for further investigation as a data curation task. Conclusion The automatic discrimination of the Class C sub-families of G protein-coupled receptors from their unaligned primary sequences shows clear limits. This study has investigated in some detail the consistency of their misclassification using random forest ensemble classifiers. Different sub-families have been shown to display very different discrimination consistency behaviors. The individual identification of consistently misclassified sequences should provide a tool for quality control to GPCR database curators.

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission.

BackgroundThe clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal.Methodology/principal findingsNon-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification.Conclusions/significanceWe show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain tumor labeling from single-voxel spectroscopy data. We are confident that the proposed methodology has wider applicability for biomedical signal processing.

BackgroundPattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation.Methodology/principal findingsA pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered.Conclusions/significanceThe unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumors, which is the difficulty of appropriately delimiting the pathological area.