Road Traffic Injuries and the Built Environment in Bogotá, Colombia, 2015-2019: A Cross-Sectional Analysis.

Nine in 10 road traffic deaths occur in low- and middle-income countries (LMICs). Despite this disproportionate burden, few studies have examined built environment correlates of road traffic injury in these settings, including in Latin America. We examined road traffic collisions in Bogotá, Colombia, occurring between 2015 and 2019, and assessed the association between neighborhood-level built environment features and pedestrian injury and death. We used descriptive statistics to characterize all police-reported road traffic collisions that occurred in Bogotá between 2015 and 2019. Cluster detection was used to identify spatial clustering of pedestrian collisions. Adjusted multivariate Poisson regression models were fit to examine associations between several neighborhood-built environment features and rate of pedestrian road traffic injury and death. A total of 173,443 police-reported traffic collisions occurred in Bogotá between 2015 and 2019. Pedestrians made up about 25% of road traffic injuries and 50% of road traffic deaths in Bogotá between 2015 and 2019. Pedestrian collisions were spatially clustered in the southwestern region of Bogotá. Neighborhoods with more street trees (RR, 0.90; 95% CI, 0.82-0.98), traffic signals (0.89, 0.81-0.99), and bus stops (0.89, 0.82-0.97) were associated with lower pedestrian road traffic deaths. Neighborhoods with greater density of large roads were associated with higher pedestrian injury. Our findings highlight the potential for pedestrian-friendly infrastructure to promote safer interactions between pedestrians and motorists in Bogotá and in similar urban contexts globally.

STRIDE: Street View-based Environmental Feature Detection and Pedestrian Collision Prediction.

This paper introduces a novel benchmark to study the impact and relationship of built environment elements on pedestrian collision prediction, intending to enhance environmental awareness in autonomous driving systems to prevent pedestrian injuries actively. We introduce a built environment detection task in large-scale panoramic images and a detection-based pedestrian collision frequency prediction task. We propose a baseline method that incorporates a collision prediction module into a state-of-the-art detection model to tackle both tasks simultaneously. Our experiments demonstrate a significant correlation between object detection of built environment elements and pedestrian collision frequency prediction. Our results are a stepping stone towards understanding the interdependencies between built environment conditions and pedestrian safety.

Rational Discovery of Antimicrobial Peptides by Means of Artificial Intelligence.

Antibiotic resistance is a worldwide public health problem due to the costs and mortality rates it generates. However, the large pharmaceutical industries have stopped searching for new antibiotics because of their low profitability, given the rapid replacement rates imposed by the increasingly observed resistance acquired by microorganisms. Alternatively, antimicrobial peptides (AMPs) have emerged as potent molecules with a much lower rate of resistance generation. The discovery of these peptides is carried out through extensive in vitro screenings of either rational or non-rational libraries. These processes are tedious and expensive and generate only a few AMP candidates, most of which fail to show the required activity and physicochemical properties for practical applications. This work proposes implementing an artificial intelligence algorithm to reduce the required experimentation and increase the efficiency of high-activity AMP discovery. Our deep learning (DL) model, called AMPs-Net, outperforms the state-of-the-art method by 8.8% in average precision. Furthermore, it is highly accurate to predict the antibacterial and antiviral capacity of a large number of AMPs. Our search led to identifying two unreported antimicrobial motifs and two novel antimicrobial peptides related to them. Moreover, by coupling DL with molecular dynamics (MD) simulations, we were able to find a multifunctional peptide with promising therapeutic effects. Our work validates our previously proposed pipeline for a more efficient rational discovery of novel AMPs.

Predicting target-ligand interactions with graph convolutional networks for interpretable pharmaceutical discovery.

Drug Discovery is an active research area that demands great investments and generates low returns due to its inherent complexity and great costs. To identify potential therapeutic candidates more effectively, we propose protein-ligand with adversarial augmentations network (PLA-Net), a deep learning-based approach to predict target-ligand interactions. PLA-Net consists of a two-module deep graph convolutional network that considers ligands' and targets' most relevant chemical information, successfully combining them to find their binding capability. Moreover, we generate adversarial data augmentations that preserve relevant biological backgrounds and improve the interpretability of our model, highlighting the relevant substructures of the ligands reported to interact with the protein targets. Our experiments demonstrate that the joint ligand-target information and the adversarial augmentations significantly increase the interaction prediction performance. PLA-Net achieves 86.52% in mean average precision for 102 target proteins with perfect performance for 30 of them, in a curated version of actives as decoys dataset. Lastly, we accurately predict pharmacologically-relevant molecules when screening the ligands of ChEMBL and drug repurposing Hub datasets with the perfect-scoring targets.

Smart pooling: AI-powered COVID-19 informative group testing.

Massive molecular testing for COVID-19 has been pointed out as fundamental to moderate the spread of the pandemic. Pooling methods can enhance testing efficiency, but they are viable only at low incidences of the disease. We propose Smart Pooling, a machine learning method that uses clinical and sociodemographic data from patients to increase the efficiency of informed Dorfman testing for COVID-19 by arranging samples into all-negative pools. To do this, we ran an automated method to train numerous machine learning models on a retrospective dataset from more than 8000 patients tested for SARS-CoV-2 from April to July 2020 in Bogotá, Colombia. We estimated the efficiency gains of using the predictor to support Dorfman testing by simulating the outcome of tests. We also computed the attainable efficiency gains of non-adaptive pooling schemes mathematically. Moreover, we measured the false-negative error rates in detecting the ORF1ab and N genes of the virus in RT-qPCR dilutions. Finally, we presented the efficiency gains of using our proposed pooling scheme on proof-of-concept pooled tests. We believe Smart Pooling will be efficient for optimizing massive testing of SARS-CoV-2.

PharmaNet: Pharmaceutical discovery with deep recurrent neural networks.

The discovery and development of novel pharmaceuticals is an area of active research mainly due to the large investments required and long payback times. As of 2016, the development of a novel drug candidate required up to $ USD 2.6 billion in investment for only 10% rate of approval by the FDA. To help decreasing the costs associated with the process, a number of in silico approaches have been developed with relatively low success due to limited predicting performance. Here, we introduced a machine learning-based algorithm as an alternative for a more accurate search of new pharmacological candidates, which takes advantage of Recurrent Neural Networks (RNN) for active molecule prediction within large databases. Our approach, termed PharmaNet was implemented here to search for ligands against specific cell receptors within 102 targets of the DUD-E database, which contains 22886 active molecules. PharmaNet comprises three main phases. First, a SMILES representation of the molecule is converted into a raw molecular image. Second, a convolutional encoder processes the data to obtain a fingerprint molecular image that is finally analyzed by a Recurrent Neural Network (RNN). This approach enables precise predictions of the molecules' target on the basis of the feature extraction, the sequence analysis and the relevant information filtered out throughout the process. Molecule Target prediction is a highly unbalanced detection problem and therefore, we propose that an adequate evaluation metric of performance is the area under the Normalized Average Precision (NAP) curve. PharmaNet largely surpasses the previous state-of-the-art method with 97.7% in the Receiver Operating Characteristic curve (ROC-AUC) and 65.5% in the NAP curve. We obtained a perfect performance for human farnesyl pyrophosphate synthase (FPPS), which is a potential target for antimicrobial and anticancer treatments. We decided to test PharmaNet for activity prediction against FPPS by searching in the CHEMBL data set. We obtained three (3) potential inhibitors that were further validated through both molecular docking and in silico toxicity prediction. Most importantly, one of this candidates, CHEMBL2007613, was predicted as a potential antiviral due to its involvement on the PCDH17 pathway, which has been reported to be related to viral infections.

Automatic seizure detection based on imaged-EEG signals through fully convolutional networks.

Seizure detection is a routine process in epilepsy units requiring manual intervention of well-trained specialists. This process could be extensive, inefficient and time-consuming, especially for long term recordings. We proposed an automatic method to detect epileptic seizures using an imaged-EEG representation of brain signals. To accomplish this, we analyzed EEG signals from two different datasets: the CHB-MIT Scalp EEG database and the EPILEPSIAE project that includes scalp and intracranial recordings. We used fully convolutional neural networks to automatically detect seizures. For our best model, we reached average accuracy and specificity values of 99.3% and 99.6%, respectively, for the CHB-MIT dataset, and corresponding values of 98.0% and 98.3% for the EPILEPSIAE patients. For these patients, the inclusion of intracranial electrodes together with scalp ones increased the average accuracy and specificity values to 99.6% and 58.3%, respectively. Regarding the other metrics, our best model reached average precision of 62.7%, recall of 58.3%, F-measure of 59.0% and AP of 54.5% on the CHB-MIT recordings, and comparatively lowers performances for the EPILEPSIAE dataset. For both databases, the number of false alarms per hour reached values less than 0.5/h for 92% of the CHB-MIT patients and less than 1.0/h for 80% of the EPILEPSIAE patients. Compared to recent studies, our lightweight approach does not need any estimation of pre-selected features and demonstrates high performances with promising possibilities for the introduction of such automatic methods in the clinical practice.

Design, Screening, and Testing of Non-Rational Peptide Libraries with Antimicrobial Activity: In Silico and Experimental Approaches.

One of the challenges of modern biotechnology is to find new routes to mitigate the resistance to conventional antibiotics. Antimicrobial peptides (AMPs) are an alternative type of biomolecules, naturally present in a wide variety of organisms, with the capacity to overcome the current microorganism resistance threat. Here, we reviewed our recent efforts to develop a new library of non-rationally produced AMPs that relies on bacterial genome inherent diversity and compared it with rationally designed libraries. Our approach is based on a four-stage workflow process that incorporates the interplay of recent developments in four major emerging technologies: artificial intelligence, molecular dynamics, surface-display in microorganisms, and microfluidics. Implementing this framework is challenging because to obtain reliable results, the in silico algorithms to search for candidate AMPs need to overcome issues of the state-of-the-art approaches that limit the possibilities for multi-space data distribution analyses in extremely large databases. We expect to tackle this challenge by using a recently developed classification algorithm based on deep learning models that rely on convolutional layers and gated recurrent units. This will be complemented by carefully tailored molecular dynamics simulations to elucidate specific interactions with lipid bilayers. Candidate AMPs will be recombinantly-expressed on the surface of microorganisms for further screening via different droplet-based microfluidic-based strategies to identify AMPs with the desired lytic abilities. We believe that the proposed approach opens opportunities for searching and screening bioactive peptides for other applications.

An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays.

In vitro scratch wound healing assay, a simple and low-cost technique that works along with other image analysis tools, is one of the most widely used 2D methods to determine the cellular migration and proliferation in processes such as regeneration and disease. There are open-source programs such as imageJ to analyze images of in vitro scratch wound healing assays, but these tools require manual tuning of various parameters, which is time-consuming and limits image throughput. For that reason, we developed an optimized plugin for imageJ to automatically recognize the wound healing size, correct the average wound width by considering its inclination, and quantify other important parameters such as: area, wound area fraction, average wound width, and width deviation of the wound images obtained from a scratch/ wound healing assay. Our plugin is easy to install and can be used with different operating systems. It can be adapted to analyze both individual images and stacks. Additionally, it allows the analysis of images obtained from bright field, phase contrast, and fluorescence microscopes. In conclusion, this new imageJ plugin is a robust tool to automatically standardize and facilitate quantification of different in vitro wound parameters with high accuracy compared with other tools and manual identification.

Automated lung cancer diagnosis using three-dimensional convolutional neural networks.

Lung cancer is the deadliest cancer worldwide. It has been shown that early detection using low-dose computer tomography (LDCT) scans can reduce deaths caused by this disease. We present a general framework for the detection of lung cancer in chest LDCT images. Our method consists of a nodule detector trained on the LIDC-IDRI dataset followed by a cancer predictor trained on the Kaggle DSB 2017 dataset and evaluated on the IEEE International Symposium on Biomedical Imaging (ISBI) 2018 Lung Nodule Malignancy Prediction test set. Our candidate extraction approach is effective to produce accurate candidates with a recall of 99.6%. In addition, our false positive reduction stage classifies successfully the candidates and increases precision by a factor of 2000. Our cancer predictor obtained a ROC AUC of 0.913 and was ranked 1st place at the ISBI 2018 Lung Nodule Malignancy Prediction challenge. Graphical abstract.