Featured Researches

Quantitative Methods

3D Deep Learning on Medical Images: A Review

The rapid advancements in machine learning, graphics processing technologies and the availability of medical imaging data have led to a rapid increase in the use of deep learning models in the medical domain. This was exacerbated by the rapid advancements in convolutional neural network (CNN) based architectures, which were adopted by the medical imaging community to assist clinicians in disease diagnosis. Since the grand success of AlexNet in 2012, CNNs have been increasingly used in medical image analysis to improve the efficiency of human clinicians. In recent years, three-dimensional (3D) CNNs have been employed for the analysis of medical images. In this paper, we trace the history of how the 3D CNN was developed from its machine learning roots, we provide a brief mathematical description of 3D CNN and provide the preprocessing steps required for medical images before feeding them to 3D CNNs. We review the significant research in the field of 3D medical imaging analysis using 3D CNNs (and its variants) in different medical areas such as classification, segmentation, detection and localization. We conclude by discussing the challenges associated with the use of 3D CNNs in the medical imaging domain (and the use of deep learning models in general) and possible future trends in the field.

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Quantitative Methods

5-HT2A mediated plasticity as a target in major depression: a narrative review connecting the dots from neurobiology to cognition and psychology

As the world's first primary morbidity factor, depression has a considerable impact on both an individual as well as a societal level. despite their discovery several decades ago, classical antidepressants have been shown to provide limited benefits against this condition. However, substances such as ketamine and psychedelics have recently shown promising results and even received the grade of Breakthrough therapy for this indication. The accurate mechanisms of action underlying the efficacy of these substances are still to be defined, but some similarities appear to be shared on different levels across these substances. These include their structural, functional and behavioral plasticity promoting abilities, as well as their capacity to promote Brain-Derived Neurotrophic Factor overexpression, which seems to constitute a key element underlying their immediate and long-lasting action. From this observation, the present review aims to examine and connect the pharmacological pathways involved in these therapies to the neurobiological, cognitive and psychological responses that could be shared by both 5-HT2AR agonists and NMDA antagonists. It is suggested that BDNF overexpression resulting from mTOR activation mediates both structural and functional plasticity, resulting in connectivity changes among high-level cognitive networks such as the Default Mode Network, finally leading to an increased and long-lasting psychological flexibility. Connecting these pieces of evidence could provide insights about their precise mechanisms of action and help researchers to develop biomarkers for antidepressant response. If the hypotheses suggested in this review are verified by further trials, they could also constitute a starting point to developing safer and more efficient antidepressants, as well as provide information about the interactions that exist between different neurotransmitters systems.

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Quantitative Methods

A Cloud connected NO2 and Ozone Sensor System for Personalized Pediatric Asthma Research and Management

This paper presents a cloud-connected indoor air quality sensor system that can be deployed to patients' homes to study personal microenvironmental exposure for asthma research and management. The system consists of multiple compact sensor units that can measure residential NO2, ozone, humidity, and temperature at one minute resolution and a cloud based informatic system that acquires, stores, and visualizes the microenvironmental data in real time. The sensor hardware can measure NO2 as low as 10 ppb and ozone at 15 ppb. The cloud informatic system is implemented using open-source software on Amazon Web Service for easy deployment and scalability. This system was successfully deployed to pediatric asthma patients' homes in a pilot study. In this study, we discovered that some families can have short term NO2 exposure higher than EPA's one hour exposure limit (100 ppb), and NO2 micropollution episodes often arise from natural gas appliance usage such as gas stove burning during cooking. By combining the personalized air pollutant exposure measurements with the physiological responses from a patient diary and medical record, this system can enable novel asthma research and personalized asthma management.

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Quantitative Methods

A Comprehensive Study of Data Augmentation Strategies for Prostate Cancer Detection in Diffusion-weighted MRI using Convolutional Neural Networks

Data augmentation refers to a group of techniques whose goal is to battle limited amount of available data to improve model generalization and push sample distribution toward the true distribution. While different augmentation strategies and their combinations have been investigated for various computer vision tasks in the context of deep learning, a specific work in the domain of medical imaging is rare and to the best of our knowledge, there has been no dedicated work on exploring the effects of various augmentation methods on the performance of deep learning models in prostate cancer detection. In this work, we have statically applied five most frequently used augmentation techniques (random rotation, horizontal flip, vertical flip, random crop, and translation) to prostate Diffusion-weighted Magnetic Resonance Imaging training dataset of 217 patients separately and evaluated the effect of each method on the accuracy of prostate cancer detection. The augmentation algorithms were applied independently to each data channel and a shallow as well as a deep Convolutional Neural Network (CNN) were trained on the five augmented sets separately. We used Area Under Receiver Operating Characteristic (ROC) curve (AUC) to evaluate the performance of the trained CNNs on a separate test set of 95 patients, using a validation set of 102 patients for finetuning. The shallow network outperformed the deep network with the best 2D slice-based AUC of 0.85 obtained by the rotation method.

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Quantitative Methods

A Compressed Sensing Approach to Pooled RT-PCR Testing for COVID-19 Detection

We propose `Tapestry', a novel approach to pooled testing with application to COVID-19 testing with quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) that can result in shorter testing time and conservation of reagents and testing kits. Tapestry combines ideas from compressed sensing and combinatorial group testing with a novel noise model for RT-PCR used for generation of synthetic data. Unlike Boolean group testing algorithms, the input is a quantitative readout from each test and the output is a list of viral loads for each sample relative to the pool with the highest viral load. While other pooling techniques require a second confirmatory assay, Tapestry obtains individual sample-level results in a single round of testing, at clinically acceptable false positive or false negative rates. We also propose designs for pooling matrices that facilitate good prediction of the infected samples while remaining practically viable. When testing n samples out of which k≪n are infected, our method needs only O(klogn) tests when using random binary pooling matrices, with high probability. However, we also use deterministic binary pooling matrices based on combinatorial design ideas of Kirkman Triple Systems to balance between good reconstruction properties and matrix sparsity for ease of pooling. In practice, we have observed the need for fewer tests with such matrices than with random pooling matrices. This makes Tapestry capable of very large savings at low prevalence rates, while simultaneously remaining viable even at prevalence rates as high as 9.5\%. Empirically we find that single-round Tapestry pooling improves over two-round Dorfman pooling by almost a factor of 2 in the number of tests required. We validate Tapestry in simulations and wet lab experiments with oligomers in quantitative RT-PCR assays. Lastly, we describe use-case scenarios for deployment.

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Quantitative Methods

A Data-driven Understanding of COVID-19 Dynamics Using Sequential Genetic Algorithm Based Probabilistic Cellular Automata

COVID-19 pandemic is severely impacting the lives of billions across the globe. Even after taking massive protective measures like nation-wide lockdowns, discontinuation of international flight services, rigorous testing etc., the infection spreading is still growing steadily, causing thousands of deaths and serious socio-economic crisis. Thus, the identification of the major factors of this infection spreading dynamics is becoming crucial to minimize impact and lifetime of COVID-19 and any future pandemic. In this work, a probabilistic cellular automata based method has been employed to model the infection dynamics for a significant number of different countries. This study proposes that for an accurate data-driven modeling of this infection spread, cellular automata provides an excellent platform, with a sequential genetic algorithm for efficiently estimating the parameters of the dynamics. To the best of our knowledge, this is the first attempt to understand and interpret COVID-19 data using optimized cellular automata, through genetic algorithm. It has been demonstrated that the proposed methodology can be flexible and robust at the same time, and can be used to model the daily active cases, total number of infected people and total death cases through systematic parameter estimation. Elaborate analyses for COVID-19 statistics of forty countries from different continents have been performed, with markedly divergent time evolution of the infection spreading because of demographic and socioeconomic factors. The substantial predictive power of this model has been established with conclusions on the key players in this pandemic dynamics.

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Quantitative Methods

A Graph Feature Auto-Encoder for the Prediction of Unobserved Node Features on Biological Networks

Motivation: Molecular interaction networks summarize complex biological processes as graphs, whose structure is informative of biological function at multiple scales. Simultaneously, omics technologies measure the variation or activity of genes, proteins, or metabolites across individuals or experimental conditions. Integrating the complementary viewpoints of biological networks and omics data is an important task in bioinformatics, but existing methods treat networks as discrete structures, which are intrinsically difficult to integrate with continuous node features or activity measures. Graph neural networks map graph nodes into a low-dimensional vector space representation, and can be trained to preserve both the local graph structure and the similarity between node features. Results: We studied the representation of transcriptional, protein-protein and genetic interaction networks in E. Coli and mouse using graph neural networks. We found that such representations explain a large proportion of variation in gene expression data, and that using gene expression data as node features improves the reconstruction of the graph from the embedding. We further proposed a new end-to-end graph feature auto-encoder which is trained on the feature reconstruction task, and showed that it performs better at predicting unobserved node features than auto-encoders that are trained on the graph reconstruction task before learning to predict node features. When applied to the problem of imputing missing data in single-cell RNAseq data, our graph feature auto-encoder outperformed a state-of-the-art imputation method that does not use protein interaction information, showing the benefit of integrating biological networks and omics data using graph representation learning.

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Quantitative Methods

A Machine Learning alternative to placebo-controlled clinical trials upon new diseases: A primer

The appearance of a new dangerous and contagious disease requires the development of a drug therapy faster than what is foreseen by usual mechanisms. Many drug therapy developments consist in investigating through different clinical trials the effects of different specific drug combinations by delivering it into a test group of ill patients, meanwhile a placebo treatment is delivered to the remaining ill patients, known as the control group. We compare the above technique to a new technique in which all patients receive a different and reasonable combination of drugs and use this outcome to feed a Neural Network. By averaging out fluctuations and recognizing different patient features, the Neural Network learns the pattern that connects the patients initial state to the outcome of the treatments and therefore can predict the best drug therapy better than the above method. In contrast to many available works, we do not study any detail of drugs composition nor interaction, but instead pose and solve the problem from a phenomenological point of view, which allows us to compare both methods. Although the conclusion is reached through mathematical modeling and is stable upon any reasonable model, this is a proof-of-concept that should be studied within other expertises before confronting a real scenario. All calculations, tools and scripts have been made open source for the community to test, modify or expand it. Finally it should be mentioned that, although the results presented here are in the context of a new disease in medical sciences, these are useful for any field that requires a experimental technique with a control group.

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Quantitative Methods

A Mathematical Description of Bacterial Chemotaxis in Response to Two Stimuli

Bacteria are often exposed to multiple stimuli in complex environments, and their efficient chemotactic decisions are critical to survive and grow in their native environments. Bacterial responses to the environmental stimuli depend on the ratio of their corresponding chemoreceptors. By incorporating the signaling machinery of individual cells, we analyze the collective motion of a population of Escherichia coli bacteria in response to two stimuli, mainly serine and methyl-aspartate (MeAsp), in a one-dimensional and a two-dimensional environment, which is inspired by experimental results in Y. Kalinin et al., J. Bacteriol. 192(7):1796-1800, 2010. Under suitable conditions, we show that if the ratio of the main chemoreceptors of individual cells, namely Tar/Tsr is less than a specific threshold, the bacteria move to the gradient of serine, and if the ratio is greater than the threshold, the group of bacteria move toward the gradient of MeAsp. Finally, we examine the theory with Monte-Carlo agent-based simulations, and verify that our results qualitatively agree well with the experimental results in Y. Kalinin et al. (2010).

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Quantitative Methods

A Minimal-Input Multilayer Perceptron for Predicting Drug-Drug Interactions Without Knowledge of Drug Structure

The necessity of predictive models in the drug discovery industry cannot be understated. With the sheer volume of potentially useful compounds that are considered for use, it is becoming increasingly computationally difficult to investigate the overlapping interactions between drugs. Understanding this is also important to the layperson who needs to know what they can and cannot mix, especially for those who use recreational drugs - which do not have the same rigorous warnings as prescription drugs. Without access to deterministic, experimental results for every drug combination, other methods are necessary to bridge this knowledge gap. Ideally, such a method would require minimal inputs, have high accuracy, and be computationally feasible. We have not come across a model that meets all these criteria. To this end, we propose a minimal-input multi-layer perceptron that predicts the interactions between two drugs. This model has a great advantage of requiring no structural knowledge of the molecules in question, and instead only uses experimentally accessible chemical and physical properties - 20 per compound in total. Using a set of known drug-drug interactions, and associated properties of the drugs involved, we trained our model on a dataset of about 650,000 entries. We report an accuracy of 0.968 on unseen samples of interactions between drugs on which the model was trained, and an accuracy of 0.942 on unseen samples of interactions between unseen drugs. We believe this to be a promising and highly extensible model that has potential for high generalized predictive accuracy with further tuning.

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