Abstract

Molecular spectroscopy studies the interaction of molecules with electromagnetic radiation, and interpreting the resultant spectra is invaluable for deducing the molecular structures. However, predicting the molecular structure from spectroscopic data is a strenuous task that requires highly specific domain knowledge. DeepSPInN is a deep reinforcement learning method that predicts the molecular structure when given Infrared and 13C Nuclear magnetic resonance spectra by formulating the molecular structure prediction problem as a Markov decision process (MDP) and employs Monte-Carlo tree search to explore and choose the actions in the formulated MDP. On the QM9 dataset, DeepSPInN is able to predict the correct molecular structure for 91.5% of the input spectra in an average time of 77 seconds for molecules with less than 10 heavy atoms. This study is the first of its kind that uses only infrared and 13C nuclear magnetic resonance spectra for molecular structure prediction without referring to any pre-existing spectral databases or molecular fragment knowledge bases, and is a leap forward in automated molecular spectral analysis.

Abstract

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19 portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19 can be accessed at http://mpds.neist.res.in:8085.

Abstract

With Cardiovascular Diseases on the rise around the world, Electrocardiograms (ECGs) play a crucial role in their diagnosis owing to their non-invasive nature and simplicity. Medical professionals typically use 12-lead ECGs for medical analysis but gathering 12-lead ECG data is an arduous task outside clinical setting. Modern wearables can collect an ECG with fewer leads than the standard 12 leads. However, medical professionals and conventional ECG analysis software find this reduced lead set data challenging to interpret. By using the reduced lead set data to create standard 12-lead ECG data, ECG reconstruction can solve this issue. This paper proposes a novel single-lead to multi-lead ECG reconstruction solution using a modified Attention U-net framework. Using only the lead II of ECG, our model is able to reproduce the other 11 leads of conventional 12-lead ECG with a Pearson correlation, Mean square error and R-squared value of 0.805, 0.0122 and 0.639, respectively. Further, a single combined model is used to reconstruct all 11 leads simultaneously, improving performance and simultaneously reducing the computational resources needed for training compared to current literature in the field. In comparison to previous works, which only reconstruct small ECG segments, our model is trained to reconstruct longer 10-second ECG signals. We demonstrate our model’s ability for real-life utilisation using a cardiovascular disease classification task. A deep learning model was trained for multi-disease classification on actual 12-lead ECG data and was tested on both original and reconstructed 12-lead ECG signals. The classification accuracies for the original and reconstructed signals were comparable, portraying that our reconstruction model can preserve diagnostically relevant artefacts in its reconstructed signals. This work provides a new promising solution in the field of single-lead ECG reconstruction, taking us a step closer to bridging the divide between reduced lead set data and existing 12-lead ECG end users like clinicians and automatic ECG classifiers.

Abstract

In this work, we describe the creation of our machine- learning-based solution for coma prognosis after cardiac arrest using longitudinal EEG and ECG recordings for the ”Predicting Neurological Recovery from Coma After Car- diac Arrest: The George B. Moody PhysioNet Challenge 2023”. Our team, “ComaToast”, had its best submission ranked 28 out of 36 teams selected worldwide, with a chal- lenge score of 0.381 on the official leaderboard for the hid- den test set. We use a combination of age and signal fea- tures from EEG and ECG recordings. Frequency domain features, specifically mean power spectral density from 4 different bands of frequencies (Delta, Theta, Alpha and Beta) and mean Burst Suppression Ratio, were extracted from pre-processed EEG recordings from the first and last available recording for a given patient. Features like mean and standard deviations were extracted along channels for ECG recordings. After imputing missing values, these fea- tures are fed to an XGBoost classifier for the final binary classification of the outcome prediction task. The features are fed to a random forest regressor to predict the CPC outcome for every patient. A solution like ours, which uses a simple model and training technique, may be more viable than deep-learning solutions in general use cases. In our final model, our approach achieved a 5-fold cross- validation score of 0.34 on the public train set.

Abstract

The discovery of potential therapeutic agents for life‑threatening diseases has become a significant problem. There is a requirement for fast and accurate methods to identify drug‑like molecules that can be used as potential candidates for novel targets. Existing techniques like high‑throughput screening and virtual screening are time‑consuming and inefficient. Traditional molecule generation pipelines are more efficient than virtual screening but use time‑consuming docking software. Such docking functions can be emulated using Machine Learning models with comparable accuracy and faster execution times. However, we find that when pre‑trained machine learning models are employed in generative pipelines as oracles, they suffer from model degradation in areas where data is scarce. In this study, we propose an active learning‑based model that can be added as a supplement to enhanced molecule generation architectures. The proposed method uses uncertainty sampling on the molecules created by the generator model and dynamically learns as the generator samples molecules from different regions of the chemical space. The proposed framework can generate molecules with high binding affinity with ∼a 70% improvement in runtime compared to the baseline model by labeling only ∼30% of molecules compared to the baseline oracle.

Abstract

In this paper, we propose MolOpt, the first attempt of its kind to use Multi-Agent Reinforcement Learning (MARL) for autonomous molecular geometry optimization (MGO). Typically MGO algorithms are hand-designed, but MolOpt uses MARL to learn a learned optimizer (policy) that can perform MGO without depending on other hand-designed optimizers. We cast MGO as a MARL problem, where each agent corresponds to a single atom in the molecule. MolOpt performs MGO by minimizing the forces on each atom in the molecule. Our experiments demonstrate the generalizing ability of MolOpt for MGO of Propane, Pentane, Heptane, Hexane, and Octane when trained on Ethane, Butane, and Isobutane. In terms of performance, MolOpt outperforms the MDMin optimizer and demonstrates similar performance to the FIRE optimizer. However, it does not surpass the BFGS optimizer. The results demonstrate that MolOpt has the potential to introduce innovative advancements in MGO by providing a novel approach using reinforcement learning (RL), which may open up new research directions for MGO. Overall, this work serves as a proof-of-concept for the potential of MARL in MGO.

Abstract

The discovery of potential therapeutic agents for life-threatening diseases has become a significant problem. There is a requirement for fast and accurate methods to identify drug-like molecules that can be used as potential candidates for novel targets. Existing techniques like high-throughput screening and virtual screening are time-consuming and inefficient. Traditional molecule generation pipelines are more efficient than virtual screening but use time-consuming docking software. Such docking functions can be emulated using Machine Learning models with comparable accuracy and faster execution times. However, we find that when pre-trained machine learning models are employed in generative pipelines as oracles, they suffer from model degradation in areas where data is scarce. In this study, we propose an active learning-based model that can be added as a supplement to enhanced molecule generation architectures. The proposed method uses uncertainty sampling on the molecules created by the generator model and dynamically learns as the generator samples molecules from different regions of the chemical space. The proposed framework can generate molecules with high binding affinity with ∼ a 70% improvement in runtime compared to the baseline model by labeling only ∼ 30% of molecules compared to the baseline oracle.

Abstract

In drug discovery applications, high throughput virtual screening exercises are rou- tinely performed to determine an initial set of candidate molecules referred to as “hits”. In such an experiment, each molecule from large small-molecule drug library is evalu- ated for physical property such as the binding affinity (docking score) against a target receptor. In real-life drug discovery experiments, the drug libraries are extremely large but still a minor representation of the essentially infinite chemical space , and evaluation

Abstract

Drug design involves the process of identifying and designing molecules that bind well to a given receptor. A vital computational component of this process is the protein–ligand interaction scoring functions that evaluate the binding ability of various molecules or ligands with a given protein receptor binding pocket reasonably accurately. With the publicly available protein–ligand binding affinity data sets in both sequential and structural forms, machine learning methods have gained traction as a top choice for developing such scoring functions. While the performance shown by these models is optimistic, there are several hidden biases present in these data sets themselves that affect the utility of such models for practical purposes such as virtual screening. In this work, we use published methods to systematically investigate several such factors or biases present in these data sets. In our analysis, we highlight the importance of considering sequence, protein–ligand interaction, and pocket structure similarity while constructing data splits and provide an explanation for good protein-only and ligand-only performances in some data sets. Through this study, we provide to the community several pointers for the design of binding affinity predictors and data sets for reliable applicability.

Abstract

X-rays diagnose numerous thoracic diseases; however, accurate pathology detection requires trained radiologists. The number of available experts may impede population-level patient care, delaying medical action. State-of-the-art (SOTA) machine learning methods categorize chest X-rays across numerous diseases well but do not always account for explainability. Interpretability assessments rarely focus on the conciseness and anatomical correctness of Class Activation Mapping outcomes. These models are not accurate or dependable when tested on different datasets of the same modality. They are not used because their predicted performance is not explainable. This work introduces a self-supervised and weakly supervised pretraining pipeline with an auxiliary loss and supervised fine-tuning that retains performance across datasets. We use the Chest X-ray14 (NIH CXR) dataset for pre-training and CheXpert