Oya Beyan

Md. Rezaul Karim, Tanhim Islam, Oya Beyan et al.

Artificial intelligence (AI) systems utilizing deep neural networks (DNNs) and machine learning (ML) algorithms are widely used for solving important problems in bioinformatics, biomedical informatics, and precision medicine. However, complex DNNs or ML models, which are often perceived as opaque and black-box, can make it difficult to understand the reasoning behind their decisions. This lack of transparency can be a challenge for both end-users and decision-makers, as well as AI developers. Additionally, in sensitive areas like healthcare, explainability and accountability are not only desirable but also legally required for AI systems that can have a significant impact on human lives. Fairness is another growing concern, as algorithmic decisions should not show bias or discrimination towards certain groups or individuals based on sensitive attributes. Explainable artificial intelligence (XAI) aims to overcome the opaqueness of black-box models and provide transparency in how AI systems make decisions. Interpretable ML models can explain how they make predictions and the factors that influence their outcomes. However, most state-of-the-art interpretable ML methods are domain-agnostic and evolved from fields like computer vision, automated reasoning, or statistics, making direct application to bioinformatics problems challenging without customization and domain-specific adaptation. In this paper, we discuss the importance of explainability in the context of bioinformatics, provide an overview of model-specific and model-agnostic interpretable ML methods and tools, and outline their potential caveats and drawbacks. Besides, we discuss how to customize existing interpretable ML methods for bioinformatics problems. Nevertheless, we demonstrate how XAI methods can improve transparency through case studies in bioimaging, cancer genomics, and text mining.

Zeyd Boukhers, Christoph Lange, Oya Beyan

Our vision paper outlines a plan to improve the future of semantic interoperability in data spaces through the application of machine learning. The use of data spaces, where data is exchanged among members in a self-regulated environment, is becoming increasingly popular. However, the current manual practices of managing metadata and vocabularies in these spaces are time-consuming, prone to errors, and may not meet the needs of all stakeholders. By leveraging the power of machine learning, we believe that semantic interoperability in data spaces can be significantly improved. This involves automatically generating and updating metadata, which results in a more flexible vocabulary that can accommodate the diverse terminologies used by different sub-communities. Our vision for the future of data spaces addresses the limitations of conventional data exchange and makes data more accessible and valuable for all members of the community.

Md. Rezaul Karim, Lina Molinas Comet, Oya Beyan et al.

Structured and unstructured data and facts about drugs, genes, protein, viruses, and their mechanism are spread across a huge number of scientific articles. These articles are a large-scale knowledge source and can have a huge impact on disseminating knowledge about the mechanisms of certain biological processes. A domain-specific knowledge graph~(KG) is an explicit conceptualization of a specific subject-matter domain represented w.r.t semantically interrelated entities and relations. A KG can be constructed by integrating such facts and data and be used for data integration, exploration, and federated queries. However, exploration and querying large-scale KGs is tedious for certain groups of users due to a lack of knowledge about underlying data assets or semantic technologies. Such a KG will not only allow deducing new knowledge and question answering(QA) but also allows domain experts to explore. Since cross-disciplinary explanations are important for accurate diagnosis, it is important to query the KG to provide interactive explanations about learned biomarkers. Inspired by these, we construct a domain-specific KG, particularly for cancer-specific biomarker discovery. The KG is constructed by integrating cancer-related knowledge and facts from multiple sources. First, we construct a domain-specific ontology, which we call OncoNet Ontology (ONO). The ONO ontology is developed to enable semantic reasoning for verification of the predictions for relations between diseases and genes. The KG is then developed and enriched by harmonizing the ONO, additional metadata schemas, ontologies, controlled vocabularies, and additional concepts from external sources using a BERT-based information extraction method. BioBERT and SciBERT are finetuned with the selected articles crawled from PubMed. We listed down some queries and some examples of QA and deducing knowledge based on the KG.

Zeyd Boukhers, Arnim Bleier, Yeliz Ucer Yediel et al.

Data privacy and ownership are significant in social data science, raising legal and ethical concerns. Sharing and analyzing data is difficult when different parties own different parts of it. An approach to this challenge is to apply de-identification or anonymization techniques to the data before collecting it for analysis. However, this can reduce data utility and increase the risk of re-identification. To address these limitations, we present PADME, a distributed analytics tool that federates model implementation and training. PADME uses a federated approach where the model is implemented and deployed by all parties and visits each data location incrementally for training. This enables the analysis of data across locations while still allowing the model to be trained as if all data were in a single location. Training the model on data in its original location preserves data ownership. Furthermore, the results are not provided until the analysis is completed on all data locations to ensure privacy and avoid bias in the results.

Zeyd Boukhers, Oya Beyan, Cong Yang et al.

Scientific knowledge on the Web is published as passive assertions and cannot decide when to validate evidence, reconcile contradictions, or update confidence as findings accumulate. Curation depends on centralised middleware and institutional continuity, but when registries close, active stewardship stops even when data remain online. We advance the concept of Autonomous FAIR Digital Objects (aFDOs) from an abstract idea to an operational model, to offer a route from passive scientific publication toward accountable, standards-aligned automation that can outlive its publishing institutions. aFDO augments FDOs with three capabilities anchored in Semantic Web standards, namely 1) a policy layer over RDF-star aligned with PROV-O, SHACL, and ODRL for portable condition-action rules, 2) an announcement layer over ActivityStreams 2.0 that bounds per-announcement evaluation cost, and 3) an agreement layer that resolves multi-source contradictions through reputation and confidence weighted agreement under a bounded adversarial model. We provide a formal definition that distinguishes policy specifications, event handlers, and communication interfaces. We evaluate an open reference implementation on 4,305 FDOs grounded in rare-disease ontologies, namely ClinVar, HPO, and Orphanet, combined with controlled synthetic observations. The consensus mechanism resolves 56.3% of 3,914 naturally occurring ClinVar conflicts where multiple submitters disagree and an expert panel has subsequently adjudicated. Under Sybil, collusion, and poisoning attacks, the mechanism degrades gracefully within its design Byzantine-tolerance bound (f < n/5), and fails as predicted beyond that bound.

Jiahui Geng, Yongli Mou, Feifei Li et al.

Unlike traditional central training, federated learning (FL) improves the performance of the global model by sharing and aggregating local models rather than local data to protect the users' privacy. Although this training approach appears secure, some research has demonstrated that an attacker can still recover private data based on the shared gradient information. This on-the-fly reconstruction attack deserves to be studied in depth because it can occur at any stage of training, whether at the beginning or at the end of model training; no relevant dataset is required and no additional models need to be trained. We break through some unrealistic assumptions and limitations to apply this reconstruction attack in a broader range of scenarios. We propose methods that can reconstruct the training data from shared gradients or weights, corresponding to the FedSGD and FedAvg usage scenarios, respectively. We propose a zero-shot approach to restore labels even if there are duplicate labels in the batch. We study the relationship between the label and image restoration. We find that image restoration fails even if there is only one incorrectly inferred label in the batch; we also find that when batch images have the same label, the corresponding image is restored as a fusion of that class of images. Our approaches are evaluated on classic image benchmarks, including CIFAR-10 and ImageNet. The batch size, image quality, and the adaptability of the label distribution of our approach exceed those of GradInversion, the state-of-the-art.

Md. Rezaul Karim, Till Döhmen, Dietrich Rebholz-Schuhmann et al.

Amid the coronavirus disease(COVID-19) pandemic, humanity experiences a rapid increase in infection numbers across the world. Challenge hospitals are faced with, in the fight against the virus, is the effective screening of incoming patients. One methodology is the assessment of chest radiography(CXR) images, which usually requires expert radiologist's knowledge. In this paper, we propose an explainable deep neural networks(DNN)-based method for automatic detection of COVID-19 symptoms from CXR images, which we call DeepCOVIDExplainer. We used 15,959 CXR images of 15,854 patients, covering normal, pneumonia, and COVID-19 cases. CXR images are first comprehensively preprocessed, before being augmented and classified with a neural ensemble method, followed by highlighting class-discriminating regions using gradient-guided class activation maps(Grad-CAM++) and layer-wise relevance propagation(LRP). Further, we provide human-interpretable explanations of the predictions. Evaluation results based on hold-out data show that our approach can identify COVID-19 confidently with a positive predictive value(PPV) of 91.6%, 92.45%, and 96.12%; precision, recall, and F1 score of 94.6%, 94.3%, and 94.6%, respectively for normal, pneumonia, and COVID-19 cases, respectively, making it comparable or improved results over recent approaches. We hope that our findings will be a useful contribution to the fight against COVID-19 and, in more general, towards an increasing acceptance and adoption of AI-assisted applications in the clinical practice.

Md. Rezaul Karim, Michael Cochez, Oya Beyan et al.

The discovery of important biomarkers is a significant step towards understanding the molecular mechanisms of carcinogenesis; enabling accurate diagnosis for, and prognosis of, a certain cancer type. Before recommending any diagnosis, genomics data such as gene expressions(GE) and clinical outcomes need to be analyzed. However, complex nature, high dimensionality, and heterogeneity in genomics data make the overall analysis challenging. Convolutional neural networks(CNN) have shown tremendous success in solving such problems. However, neural network models are perceived mostly as `black box' methods because of their not well-understood internal functioning. However, interpretability is important to provide insights on why a given cancer case has a certain type. Besides, finding the most important biomarkers can help in recommending more accurate treatments and drug repositioning. In this paper, we propose a new approach called OncoNetExplainer to make explainable predictions of cancer types based on GE data. We used genomics data about 9,074 cancer patients covering 33 different cancer types from the Pan-Cancer Atlas on which we trained CNN and VGG16 networks using guided-gradient class activation maps++(GradCAM++). Further, we generate class-specific heat maps to identify significant biomarkers and computed feature importance in terms of mean absolute impact to rank top genes across all the cancer types. Quantitative and qualitative analyses show that both models exhibit high confidence at predicting the cancer types correctly giving an average precision of 96.25%. To provide comparisons with the baselines, we identified top genes, and cancer-specific driver genes using gradient boosted trees and SHapley Additive exPlanations(SHAP). Finally, our findings were validated with the annotations provided by the TumorPortal.

Md. Rezaul Karim, Michael Cochez, Joao Bosco Jares et al.

Interference between pharmacological substances can cause serious medical injuries. Correctly predicting so-called drug-drug interactions (DDI) does not only reduce these cases but can also result in a reduction of drug development cost. Presently, most drug-related knowledge is the result of clinical evaluations and post-marketing surveillance; resulting in a limited amount of information. Existing data-driven prediction approaches for DDIs typically rely on a single source of information, while using information from multiple sources would help improve predictions. Machine learning (ML) techniques are used, but the techniques are often unable to deal with skewness in the data. Hence, we propose a new ML approach for predicting DDIs based on multiple data sources. For this task, we use 12,000 drug features from DrugBank, PharmGKB, and KEGG drugs, which are integrated using Knowledge Graphs (KGs). To train our prediction model, we first embed the nodes in the graph using various embedding approaches. We found that the best performing combination was a ComplEx embedding method creating using PyTorch-BigGraph (PBG) with a Convolutional-LSTM network and classic machine learning-based prediction models. The model averaging ensemble method of three best classifiers yields up to 0.94, 0.92, 0.80 for AUPR, F1-score, and MCC, respectively during 5-fold cross-validation tests.

Md. Rezaul Karim, Michael Cochez, Achille Zappa et al.

The study of genetic variants can help find correlating population groups to identify cohorts that are predisposed to common diseases and explain differences in disease susceptibility and how patients react to drugs. Machine learning algorithms are increasingly being applied to identify interacting GVs to understand their complex phenotypic traits. Since the performance of a learning algorithm not only depends on the size and nature of the data but also on the quality of underlying representation, deep neural networks can learn non-linear mappings that allow transforming GVs data into more clustering and classification friendly representations than manual feature selection. In this paper, we proposed convolutional embedded networks in which we combine two DNN architectures called convolutional embedded clustering and convolutional autoencoder classifier for clustering individuals and predicting geographic ethnicity based on GVs, respectively. We employed CAE-based representation learning on 95 million GVs from the 1000 genomes and Simons genome diversity projects. Quantitative and qualitative analyses with a focus on accuracy and scalability show that our approach outperforms state-of-the-art approaches such as VariantSpark and ADMIXTURE. In particular, CEC can cluster targeted population groups in 22 hours with an adjusted rand index of 0.915, the normalized mutual information of 0.92, and the clustering accuracy of 89%. Contrarily, the CAE classifier can predict the geographic ethnicity of unknown samples with an F1 and Mathews correlation coefficient(MCC) score of 0.9004 and 0.8245, respectively. To provide interpretations of the predictions, we identify significant biomarkers using gradient boosted trees(GBT) and SHAP. Overall, our approach is transparent and faster than the baseline methods, and scalable for 5% to 100% of the full human genome.