A comprehensive review of machine learning techniques for multi-omics data integration: challenges and applications in precision oncology.

Multi-omics data play a crucial role in precision medicine, mainly to understand the diverse biological interaction between different omics. Machine learning approaches have been extensively employed in this context over the years. This review aims to comprehensively summarize and categorize these advancements, focusing on the integration of multi-omics data, which includes genomics, transcriptomics, proteomics and metabolomics, alongside clinical data. We discuss various machine learning techniques and computational methodologies used for integrating distinct omics datasets and provide valuable insights into their application. The review emphasizes both the challenges and opportunities present in multi-omics data integration, precision medicine and patient stratification, offering practical recommendations for method selection in various scenarios. Recent advances in deep learning and network-based approaches are also explored, highlighting their potential to harmonize diverse biological information layers. Additionally, we present a roadmap for the integration of multi-omics data in precision oncology, outlining the advantages, challenges and implementation difficulties. Hence this review offers a thorough overview of current literature, providing researchers with insights into machine learning techniques for patient stratification, particularly in precision oncology. Contact:  anirban@klyuniv.ac.in.

Sliding Window Optimal Transport for Open World Artifact Detection in Histopathology.

Histological images are frequently impaired by local artifacts from scanner malfunctions or iatrogenic processes - caused by preparation - impacting the performance of Deep Learning models. Models often struggle with the slightest out-of-distribution shifts, resulting in compromised performance. Detecting artifacts and failure modes of the models is crucial to ensure open-world applicability to whole slide images for tasks like segmentation or diagnosis. We introduce a novel technique for out-of-distribution detection within whole slide images, compatible with any segmentation or classification model. Our approach tiles multi-layer features into sliding window patches and leverages optimal transport to align them with recognized in-distribution samples. We average the optimal transport costs over tiles and layers to detect out-of-distribution samples. Notably, our method excels in identifying failure modes that would harm downstream performance, surpassing contemporary out-of-distribution detection techniques. We evaluate our method for both natural and synthetic artifacts, considering distribution shifts of various sizes and types. The results confirm that our technique outperforms alternative methods for artifact detection. We assess our method components and the ability to negate the impact of artifacts on the downstream tasks. Finally, we demonstrate that our method can mitigate the risk of performance drops in downstream tasks, enhancing reliability by up to 77%. In testing 7 annotated whole slide images with natural artifacts, our method boosted the Dice score by 68%, highlighting its real open-world utility.

A randomized optimal k-mer indexing approach for efficient parallel genome sequence compression.

Next Generation Sequencing (NGS) technology generates massive amounts of genome sequence that increases rapidly over time. As a result, there is a growing need for efficient compression algorithms to facilitate the processing, storage, transmission, and analysis of large-scale genome sequences. Over the past 31 years, numerous state-of-the-art compression algorithms have been developed. The performance of any compression algorithm is measured by three main compression metrics: compression ratio, time, and memory usage. Existing k-mer hash indexing systems take more time, due to the decision-making process based on compression results. In this paper, we propose a two-phase reference genome compression algorithm using optimal k-mer length (RGCOK). Reference-based compression takes advantage of the inter-similarity between chromosomes of the same species. RGCOK achieves this by finding the optimal k-mer length for matching, using a randomization method and hashing. The performance of RGCOK was evaluated on three different benchmark data sets: novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Homo sapiens, and other species sequences using an Amazon AWS virtual cloud machine. Experiments showed that the optimal k-mer finding time by RGCOK is around 45.28 min, whereas the time for existing state-of-the-art algorithms HiRGC, SCCG, and HRCM ranges from 58 min to 8.97 h.

Closing the loop for AI-ready radiology.

BACKGROUND: In recent years, AI has made significant advancements in medical diagnosis and prognosis. However, the incorporation of AI into clinical practice is still challenging and under-appreciated. We aim to demonstrate a possible vertical integration approach to close the loop for AI-ready radiology. METHOD: This study highlights the importance of two-way communication for AI-assisted radiology. As a key part of the methodology, it demonstrates the integration of AI systems into clinical practice with structured reports and AI visualization, giving more insight into the AI system. By integrating cooperative lifelong learning into the AI system, we ensure the long-term effectiveness of the AI system, while keeping the radiologist in the loop.  RESULTS: We demonstrate the use of lifelong learning for AI systems by incorporating AI visualization and structured reports. We evaluate Memory Aware-Synapses and Rehearsal approach and find that both approaches work in practice. Furthermore, we see the advantage of lifelong learning algorithms that do not require the storing or maintaining of samples from previous datasets. CONCLUSION: In conclusion, incorporating AI into the clinical routine of radiology requires a two-way communication approach and seamless integration of the AI system, which we achieve with structured reports and visualization of the insight gained by the model. Closing the loop for radiology leads to successful integration, enabling lifelong learning for the AI system, which is crucial for sustainable long-term performance. KEY POINTS: · The integration of AI systems into the clinical routine with structured reports and AI visualization.. · Two-way communication between AI and radiologists is necessary to enable AI that keeps the radiologist in the loop.. · Closing the loop enables lifelong learning, which is crucial for long-term, high-performing AI in radiology..

Comparison of Ultra-High-Resolution and Normal-Resolution CT-Angiography for Intracranial Aneurysm Detection in Patients with Subarachnoid Hemorrhage.

RATIONALE AND OBJECTIVES: Ruptured intracranial aneurysms (IAs) are the leading cause for atraumatic subarachnoid hemorrhage. In case of aneurysm rupture, patients may face life-threatening complications and require aneurysm occlusion. Detection of the aneurysm in computed tomography (CT) imaging is therefore essential for patient outcome. This study provides an evaluation of the diagnostic accuracy of Ultra-High-Resolution Computed Tomography Angiography (UHR-CTA) and Normal-Resolution Computed Tomography Angiography (NR-CTA) concerning IA detection and characterization. MATERIALS AND METHODS: Consecutive patients with atraumatic subarachnoid hemorrhage who received Digital Subtraction Angiography (DSA) and either UHR-CTA or NR-CTA were retrospectively included. Three readers evaluated CT-Angiography regarding image quality, diagnostic confidence and presence of IAs. Sensitivity and specificity were calculated on patient-level and segment-level with reference standard DSA-imaging. CTA patient radiation exposure (effective dose) was compared. RESULTS: One hundred and eight patients were identified (mean age = 57.8 ±â€¯14.1 years, 65 women). UHR-CTA revealed significantly higher image quality and diagnostic confidence (P < 0.001) for all readers and significantly lower effective dose (P < 0.001). Readers correctly classified ≥55/56 patients on UHR-CTA and ≥44/52 patients on NR-CTA. We noted significantly higher patient-level sensitivity for UHR-CTA compared to NR-CTA for all three readers (reader 1: 41/41 [100%] vs. 28/34 [82%], reader 2: 41/41 [100%] vs. 30/34 [88%], reader 3: 41/41 [100%] vs. 30/34 [88%], P ≤ 0.04). Segment-level analysis also revealed significantly higher sensitivity for UHR-CTA compared to NR-CTA for all three readers (reader 1: 47/49 [96%] vs. 34/45 [76%], reader 2: 47/49 [96%] vs. 37/45 [82%], reader 3: 48/49 [98%] vs. 37/45 [82%], P ≤ 0.04). Specificity was comparable for both techniques. CONCLUSION: We found Ultra-High-Resolution CT-Angiography to provide higher sensitivity than Normal-Resolution CT-Angiography for the detection of intracranial aneurysms in patients with aneurysmal subarachnoid hemorrhage while improving image quality and reducing patient radiation exposure.

Leveraging Attention-Based Convolutional Neural Networks for Meningioma Classification in Computational Histopathology.

Convolutional neural networks (CNNs) are becoming increasingly valuable tools for advanced computational histopathology, promoting precision medicine through exceptional visual decoding abilities. Meningiomas, the most prevalent primary intracranial tumors, necessitate accurate grading and classification for informed clinical decision-making. Recently, DNA methylation-based molecular classification of meningiomas has proven to be more effective in predicting tumor recurrence than traditional histopathological methods. However, DNA methylation profiling is expensive, labor-intensive, and not widely accessible. Consequently, a digital histology-based prediction of DNA methylation classes would be advantageous, complementing molecular classification. In this study, we developed and rigorously assessed an attention-based multiple-instance deep neural network for predicting meningioma methylation classes using tumor methylome data from 142 (+51) patients and corresponding hematoxylin-eosin-stained histological sections. Pairwise analysis of sample cohorts from three meningioma methylation classes demonstrated high accuracy in two combinations. The performance of our approach was validated using an independent set of 51 meningioma patient samples. Importantly, attention map visualization revealed that the algorithm primarily focuses on tumor regions deemed significant by neuropathologists, offering insights into the decision-making process of the CNN. Our findings highlight the capacity of CNNs to effectively harness phenotypic information from histological sections through computerized images for precision medicine. Notably, this study is the first demonstration of predicting clinically relevant DNA methylome information using computer vision applied to standard histopathology. The introduced AI framework holds great potential in supporting, augmenting, and expediting meningioma classification in the future.

Artificial Intelligence-Based Tool for Tumor Detection and Quantitative Tissue Analysis in Colorectal Specimens.

Digital pathology adoption allows for applying computational algorithms to routine pathology tasks. Our study aimed to develop a clinical-grade artificial intelligence (AI) tool for precise multiclass tissue segmentation in colorectal specimens (resections and biopsies) and clinically validate the tool for tumor detection in biopsy specimens. The training data set included 241 precisely manually annotated whole-slide images (WSIs) from multiple institutions. The algorithm was trained for semantic segmentation of 11 tissue classes with an additional module for biopsy WSI classification. Six case cohorts from 5 pathology departments (4 countries) were used for formal and clinical validation, digitized by 4 different scanning systems. The developed algorithm showed high precision of segmentation of different tissue classes in colorectal specimens with composite multiclass Dice score of up to 0.895 and pixel-wise tumor detection specificity and sensitivity of up to 0.958 and 0.987, respectively. In the clinical validation study on multiple external cohorts, the AI tool reached sensitivity of 1.0 and specificity of up to 0.969 for tumor detection in biopsy WSI. The AI tool analyzes most biopsy cases in less than 1 minute, allowing effective integration into clinical routine. We developed and extensively validated a highly accurate, clinical-grade tool for assistive diagnostic processing of colorectal specimens. This tool allows for quantitative deciphering of colorectal cancer tissue for development of prognostic and predictive biomarkers and personalization of oncologic care. This study is a foundation for a SemiCOL computational challenge. We open-source multiple manually annotated and weakly labeled test data sets, representing a significant contribution to the colorectal cancer computational pathology field.

Lifelong nnU-Net: a framework for standardized medical continual learning.

As the enthusiasm surrounding Deep Learning grows, both medical practitioners and regulatory bodies are exploring ways to safely introduce image segmentation in clinical practice. One frontier to overcome when translating promising research into the clinical open world is the shift from static to continual learning. Continual learning, the practice of training models throughout their lifecycle, is seeing growing interest but is still in its infancy in healthcare. We present Lifelong nnU-Net, a standardized framework that places continual segmentation at the hands of researchers and clinicians. Built on top of the nnU-Net-widely regarded as the best-performing segmenter for multiple medical applications-and equipped with all necessary modules for training and testing models sequentially, we ensure broad applicability and lower the barrier to evaluating new methods in a continual fashion. Our benchmark results across three medical segmentation use cases and five continual learning methods give a comprehensive outlook on the current state of the field and signify a first reproducible benchmark.

Ultra-High-Resolution CT of the Head and Neck with Deep Learning Reconstruction-Assessment of Image Quality and Radiation Exposure and Intraindividual Comparison with Normal-Resolution CT.

OBJECTIVES: To assess the benefits of ultra-high-resolution CT (UHR-CT) with deep learning-based image reconstruction engine (AiCE) regarding image quality and radiation dose and intraindividually compare it to normal-resolution CT (NR-CT). METHODS: Forty consecutive patients with head and neck UHR-CT with AiCE for diagnosed head and neck malignancies and available prior NR-CT of a different scanner were retrospectively evaluated. Two readers evaluated subjective image quality using a 5-point Likert scale regarding image noise, image sharpness, artifacts, diagnostic acceptability, and assessability of various anatomic regions. For reproducibility, inter-reader agreement was analyzed. Furthermore, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and slope of the gray-value transition between different tissues were calculated. Radiation dose was evaluated by comparing CTDIvol, DLP, and mean effective dose values. RESULTS: UHR-CT with AiCE reconstruction led to significant improvement in subjective (image noise and diagnostic acceptability: p < 0.000; ICC ≥ 0.91) and objective image quality (SNR: p < 0.000; CNR: p < 0.025) at significantly lower radiation doses (NR-CT 2.03 ± 0.14 mSv; UHR-CT 1.45 ± 0.11 mSv; p < 0.0001) compared to NR-CT. CONCLUSIONS: Compared to NR-CT, UHR-CT combined with AiCE provides superior image quality at a markedly lower radiation dose. With improved soft tissue assessment and potentially improved tumor detection, UHR-CT may add further value to the role of CT in the assessment of head and neck pathologies.

HEX: a safe research framework for hybrid EMT X-ray navigation.

PURPOSE: Navigating with continuous X-ray provides visual guidance, but exposes both surgeon and patient to ionizing radiation, which is associated with serious health risks. Interleaving fluoro snapshots with electromagnetic tracking (EMT) potentially minimizes radiation. METHODS: We propose hybrid EMT + X-ray (HEX), a research framework for navigation with an emphasis on safe experimentation. HEX is based on several hardware and software components that are orchestrated to allow for safe and efficient data acquisition. RESULTS: In our study, hybrid navigation reduces radiation by [Formula: see text] with cubic, and by [Formula: see text] with linear error compensation while achieving submillimeter accuracy. Training points for compensation can be reduced by half while keeping a similar accuracy-radiation trade-off. CONCLUSION: The HEX framework allows to safely and efficiently evaluate the hybrid navigation approach in simulated procedures. Complementing intraoperative X-ray with EMT significantly reduces radiation in the OR, increasing the safety of patients and surgeons.

Temporally consistent sequence-to-sequence translation of cataract surgeries.

PURPOSE: Image-to-image translation methods can address the lack of diversity in publicly available cataract surgery data. However, applying image-to-image translation to videos-which are frequently used in medical downstream applications-induces artifacts. Additional spatio-temporal constraints are needed to produce realistic translations and improve the temporal consistency of translated image sequences. METHODS: We introduce a motion-translation module that translates optical flows between domains to impose such constraints. We combine it with a shared latent space translation model to improve image quality. Evaluations are conducted regarding translated sequences' image quality and temporal consistency, where we propose novel quantitative metrics for the latter. Finally, the downstream task of surgical phase classification is evaluated when retraining it with additional synthetic translated data. RESULTS: Our proposed method produces more consistent translations than state-of-the-art baselines. Moreover, it stays competitive in terms of the per-image translation quality. We further show the benefit of consistently translated cataract surgery sequences for improving the downstream task of surgical phase prediction. CONCLUSION: The proposed module increases the temporal consistency of translated sequences. Furthermore, imposed temporal constraints increase the usability of translated data in downstream tasks. This allows overcoming some of the hurdles of surgical data acquisition and annotation and enables improving models' performance by translating between existing datasets of sequential frames.

Significance of an altered lncRNA landscape in schizophrenia and cognition: clues from a case-control association study.

Genetic etiology of schizophrenia is poorly understood despite large genome-wide association data. Long non-coding RNAs (lncRNAs) with a probable regulatory role are emerging as important players in neuro-psychiatric disorders including schizophrenia. Prioritising important lncRNAs and analyses of their holistic interaction with their target genes may provide insights into disease biology/etiology. Of the 3843 lncRNA SNPs reported in schizophrenia GWASs extracted using lincSNP 2.0, we prioritised n = 247 based on association strength, minor allele frequency and regulatory potential and mapped them to lncRNAs. lncRNAs were then prioritised based on their expression in brain using lncRBase, epigenetic role using 3D SNP and functional relevance to schizophrenia etiology. 18 SNPs were finally tested for association with schizophrenia (n = 930) and its endophenotypes-tardive dyskinesia (n = 176) and cognition (n = 565) using a case-control approach. Associated SNPs were characterised by ChIP seq, eQTL, and transcription factor binding site (TFBS) data using FeatSNP. Of the eight SNPs significantly associated, rs2072806 in lncRNA hsaLB_IO39983 with regulatory effect on BTN3A2 was associated with schizophrenia (p = 0.006); rs2710323 in hsaLB_IO_2331 with role in dysregulation of ITIH1 with tardive dyskinesia (p < 0.05); and four SNPs with significant cognition score reduction (p < 0.05) in cases. Two of these with two additional variants in eQTL were observed among controls (p < 0.05), acting likely as enhancer SNPs and/or altering TFBS of eQTL mapped downstream genes. This study highlights important lncRNAs in schizophrenia and provides a proof of concept of novel interactions of lncRNAs with protein-coding genes to elicit alterations in immune/inflammatory pathways of schizophrenia.

Artificial intelligence for tumour tissue detection and histological regression grading in oesophageal adenocarcinomas: a retrospective algorithm development and validation study.

BACKGROUND: Oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction are among the most common malignant epithelial tumours. Most patients receive neoadjuvant therapy before complete tumour resection. Histological assessment after resection includes identification of residual tumour tissue and areas of regressive tumour, data which are used to calculate a clinically relevant regression score. We developed an artificial intelligence (AI) algorithm for tumour tissue detection and tumour regression grading in surgical specimens from patients with oesophageal adenocarcinoma or adenocarcinoma of the oesophagogastric junction. METHODS: We used one training cohort and four independent test cohorts to develop, train, and validate a deep learning tool. The material consisted of histological slides from surgically resected specimens from patients with oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction from three pathology institutes (two in Germany, one in Austria) and oesophageal cancer cohort of The Cancer Genome Atlas (TCGA). All slides were from neoadjuvantly treated patients except for those from the TCGA cohort, who were neoadjuvant-therapy naive. Data from training cohort and test cohort cases were extensively manually annotated for 11 tissue classes. A convolutional neural network was trained on the data using a supervised principle. First, the tool was formally validated using manually annotated test datasets. Next, tumour regression grading was assessed in a retrospective cohort of post-neoadjuvant therapy surgical specimens. The grading of the algorithm was compared with that of a group of 12 board-certified pathologists from one department. To further validate the tool, three pathologists processed whole resection cases with and without AI assistance. FINDINGS: Of the four test cohorts, one included 22 manually annotated histological slides (n=20 patients), one included 62 sides (n=15), one included 214 slides (n=69), and the final one included 22 manually annotated histological slides (n=22). In the independent test cohorts the AI tool had high patch-level accuracy for identifying both tumour and regression tissue. When we validated the concordance of the AI tool against analyses by a group of pathologists (n=12), agreement was 63·6% (quadratic kappa 0·749; p<0·0001) at case level. The AI-based regression grading triggered true reclassification of resected tumour slides in seven cases (including six cases who had small tumour regions that were initially missed by pathologists). Use of the AI tool by three pathologists increased interobserver agreement and substantially reduced diagnostic time per case compared with working without AI assistance. INTERPRETATION: Use of our AI tool in the diagnostics of oesophageal adenocarcinoma resection specimens by pathologists increased diagnostic accuracy, interobserver concordance, and significantly reduced assessment time. Prospective validation of the tool is required. FUNDING: North Rhine-Westphalia state, Federal Ministry of Education and Research of Germany, and the Wilhelm Sander Foundation.

A Survey on Shape-Constraint Deep Learning for Medical Image Segmentation.

Since the advent of U-Net, fully convolutional deep neural networks and its many variants have completely changed the modern landscape of deep-learning based medical image segmentation. However, the over-dependence of these methods on pixel-level classification and regression has been identified early on as a problem. Especially when trained on medical databases with sparse available annotation, these methods are prone to generate segmentation artifacts such as fragmented structures, topological inconsistencies and islands of pixel. These artifacts are especially problematic in medical imaging since segmentation is almost always a pre-processing step for some downstream evaluations like surgical planning, visualization, prognosis, or treatment planning. However, one common thread across all these downstream tasks is the demand of anatomical consistency. To ensure the segmentation result is anatomically consistent, approaches based on Markov/ Conditional Random Fields, Statistical Shape Models, Active Contours are becoming increasingly popular over the past 5 years. In this review paper, a broad overview of recent literature on bringing explicit anatomical constraints for medical image segmentation is given, the shortcomings and opportunities are discussed and the potential shift towards implicit shape modelling is elaborated. We review the most relevant papers published until the submission date and provide a tabulated view with method details for quick access.

Inducing consumers to use calorie information: a multinational investigation.

OBJECTIVE: We identify individuals who set daily intake budgets and examine if an intervention making people estimate their calorie intake up to a certain point in the day helps those setting daily budgets to regulate their calorie intake for the remainder of the day, after high prior consumption. DESIGN: We conducted an online experiment in five countries: Australia, China, Germany, India, and the UK (n = 3,032) using a 2 (setting calorie budget: yes vs. no, measured) x 2 (intervention: intake reminder vs. control, manipulated) between-subjects design, with the amount of prior consumption measured. Participants were contacted in the afternoon. Those in the intervention condition were asked to estimate their prior calorie intake on that day. MAIN OUTCOME MEASURES: We measured the individual characteristics of those who set daily calorie budgets and the intended calorie intake for the remainder of the day. RESULTS: Among people who set daily calorie budgets, the intervention reduced intended calorie intake for the remainder of the day by 176 calories if they had already consumed a high amount of calories that day. CONCLUSION: A timely intervention to estimate one's calorie intake can lower additional intended calorie intake among those who set daily calorie budget.

Deep variational graph autoencoders for novel host-directed therapy options against COVID-19.

The COVID-19 pandemic has been keeping asking urgent questions with respect to therapeutic options. Existing drugs that can be repurposed promise rapid implementation in practice because of their prior approval. Conceivably, there is still room for substantial improvement, because most advanced artificial intelligence techniques for screening drug repositories have not been exploited so far. We construct a comprehensive network by combining year-long curated drug-protein/protein-protein interaction data on the one hand, and most recent SARS-CoV-2 protein interaction data on the other hand. We learn the structure of the resulting encompassing molecular interaction network and predict missing links using variational graph autoencoders (VGAEs), as a most advanced deep learning technique that has not been explored so far. We focus on hitherto unknown links between drugs and human proteins that play key roles in the replication cycle of SARS-CoV-2. Thereby, we establish novel host-directed therapy (HDT) options whose utmost plausibility is confirmed by realistic simulations. As a consequence, many of the predicted links are likely to be crucial for the virus to thrive on the one hand, and can be targeted with existing drugs on the other hand.

Psychological and behavioral responses to the declaration of COVID-19 as a pandemic: A comparative study of Hong Kong, Singapore, and the U.S.

What is the effect of declaring a pandemic? This research assesses behavioral and psychological responses to the WHO declaration of the COVID-19 pandemic, in Hong Kong, Singapore, and the U.S. We surveyed 3,032 members of the general public in these three regions about the preventative actions they were taking and their worries related to COVID-19. The WHO announcement on March 11th, 2020 created a quasi-experimental test of responses immediately before versus after the announcement. The declaration of the pandemic increased worries about the capacity of the local healthcare system in each region, as well as the proportion of people engaging in preventative actions, including actions not recommended by medical professionals. The number of actions taken correlates positively with anxiety and worries. Declaring the COVID-19 crisis as a pandemic had tangible effects-positive (increased community engagement) and negative (increased generalized anxiety)-which manifested differently across regions in line with expectancy disconfirmation theory.

Distance-based detection of out-of-distribution silent failures for Covid-19 lung lesion segmentation.

Automatic segmentation of ground glass opacities and consolidations in chest computer tomography (CT) scans can potentially ease the burden of radiologists during times of high resource utilisation. However, deep learning models are not trusted in the clinical routine due to failing silently on out-of-distribution (OOD) data. We propose a lightweight OOD detection method that leverages the Mahalanobis distance in the feature space and seamlessly integrates into state-of-the-art segmentation pipelines. The simple approach can even augment pre-trained models with clinically relevant uncertainty quantification. We validate our method across four chest CT distribution shifts and two magnetic resonance imaging applications, namely segmentation of the hippocampus and the prostate. Our results show that the proposed method effectively detects far- and near-OOD samples across all explored scenarios.

A network biology approach to identify crucial host targets for COVID-19.

The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.

Fuzzy association analysis for identifying climatic and socio-demographic factors impacting the spread of COVID-19.

Recently, the whole world witnessed the fatal outbreak of COVID-19 epidemic originating at Wuhan, Hubei province, China, during a mass gathering in a film festival. World Health Organization (WHO) has declared this COVID-19 as a pandemic due to its rapid spread across different countries within a few days. Several research works are being performed to understand the various influential factors responsible for spreading COVID. However, limited studies have been performed on how climatic and socio-demographic conditions may impact the spread of the virus. In this work, we aim to find the relationship of socio-demographic conditions, such as temperature, humidity, and population density of the regions, with the spread of COVID-19. The COVID data for different countries along with the social data are collected. For the experimental purpose, Fuzzy association rule mining is employed to infer the various relationships from the data. Moreover, to examine the seasonal effect, a streaming setting is also considered. The experimental results demonstrate various interesting insights to understand the impact of different factors on spreading COVID-19.