Comparative analysis of molecular fingerprints in prediction of drug combination effects

bbab291Application of machine and deep learning methods in drug discovery and cancer research has gained a considerable amount of attention in the past years. As the field grows, it becomes crucial to systematically evaluate the performance of novel computational solutions in relation to established techniques. To this end, we compare rule-based and data-driven molecular representations in prediction of drug combination sensitivity and drug synergy scores using standardized results of 14 high-throughput screening studies, comprising 64 200 unique combinations of 4153 molecules tested in 112 cancer cell lines. We evaluate the clustering performance of molecular representations and quantify their similarity by adapting the Centered Kernel Alignment metric. Our work demonstrates that to identify an optimal molecular representation type, it is necessary to supplement quantitative benchmark results with qualitative considerations, such as model interpretability and robustness, which may vary between and throughout preclinical drug development projects.Peer reviewe

Neural Approximate Sufficient Statistics for Implicit Models

We consider the fundamental problem of how to automatically construct summary statistics for implicit generative models where the evaluation of the likelihood function is intractable, but sampling data from the model is possible. The idea is to frame the task of constructing sufficient statistics as learning mutual information maximizing representations of the data with the help of deep neural networks. The infomax learning procedure does not need to estimate any density or density ratio. We apply our approach to both traditional approximate Bayesian computation and recent neural likelihood methods, boosting their performance on a range of tasks.Comment: ICLR2021 spotligh

Multiparameter Persistent Homology for Molecular Property Prediction

In this study, we present a novel molecular fingerprint generation method based on multiparameter persistent homology. This approach reveals the latent structures and relationships within molecular geometry, and detects topological features that exhibit persistence across multiple scales along multiple parameters, such as atomic mass, partial charge, and bond type, and can be further enhanced by incorporating additional parameters like ionization energy, electron affinity, chirality and orbital hybridization. The proposed fingerprinting method provides fresh perspectives on molecular structure that are not easily discernible from single-parameter or single-scale analysis. Besides, in comparison with traditional graph neural networks, multiparameter persistent homology has the advantage of providing a more comprehensive and interpretable characterization of the topology of the molecular data. We have established theoretical stability guarantees for multiparameter persistent homology, and have conducted extensive experiments on the Lipophilicity, FreeSolv, and ESOL datasets to demonstrate its effectiveness in predicting molecular properties.Comment: ICLR 2023-Machine Learning for Drug Discovery. arXiv admin note: text overlap with arXiv:2211.0380

Local online learning of coherent information

One of the goals of perception is to learn to respond to coherence across space, time and modality. Here we present an abstract framework for the local online unsupervised learning of this coherent information using multi-stream neural networks. The processing units distinguish between feedforward inputs projected from the environment and the lateral, contextual inputs projected from the processing units of other streams. The contextual inputs are used to guide learning towards coherent cross-stream structure. The goal of all the learning algorithms described is to maximize the predictability between each unit output and its context. Many local cost functions may be applied: e.g. mutual information, relative entropy, squared error and covariance. Theoretical and simulation results indicate that, of these, the covariance rule (1) is the only rule that specifically links and learns only those streams with coherent information, (2) can be robustly approximated by a Hebbian rule, (3) is stable with input noise, no pairwise input correlations, and in the discovery of locally less informative components that are coherent globally. In accordance with the parallel nature of the biological substrate, we also show that all the rules scale up with the number of streams

Computational role of sleep in memory reorganization

Sleep is considered to play an essential role in memory reorganization. Despite its importance, classical theoretical models did not focus on some sleep characteristics. Here, we review recent theoretical approaches investigating their roles in learning and discuss the possibility that non-rapid eye movement (NREM) sleep selectively consolidates memory, and rapid eye movement (REM) sleep reorganizes the representations of memories. We first review the possibility that slow waves during NREM sleep contribute to memory selection by using sequential firing patterns and the existence of up and down states. Second, we discuss the role of dreaming during REM sleep in developing neuronal representations. We finally discuss how to develop these points further, emphasizing the connections to experimental neuroscience and machine learning.Comment: Accepted for publication in Current Opinion in Neurobiolog

Predictive analysis of auditory attention from physiological signals

In recent years, there has been considerable interest in recording physiological signals from the human body to investigate various responses. Attention is one of the key aspects that physiologists, neuroscientists, and engineers have been exploring. Many theories have been established on auditory and visual selective attention. To date, the number of studies investigating the physiological responses of the human body to auditory attention on natural speech is, surprisingly, very limited, and there is a lack of public datasets. Investigating such physiological responses can open the door to new opportunities, as auditory attention plays a key role in many cognitive functionalities, thus impacting on learning and general task performance. In this thesis, we investigated auditory attention on the natural speech by processing physiological signals such as Electroencephalogram (EEG), Galvanic Skin Response (GSR), and Photoplethysmogram (PPG). An experiment was designed based on the well established dichotic listening task. In the experiment, we presented an audio stimulus under different auditory conditions: background noise level, length, and semanticity of the audio message. The experiment was conducted with 25 healthy, non-native speakers. The attention score was computed by counting the number of correctly identified words in the transcribed text response. All the physiological signals were labeled with their auditory condition and attention score. We formulated four predictive tasks exploiting the collected signals: Attention score, Noise level, Semanticity, and LWR (Listening, Writing, Resting, i.e., the state of the participant). In the first part, we analysed all the user text responses collected in the experiment. The statistical analysis reveals a strong dependency of the attention level on the auditory conditions. By applying hierarchical clustering, we could identify the experimental conditions that have similar effects on attention score. Significantly, the effect of semanticity appeared to vanish under high background noise. Then, analysing the signals, we found that the-state-of-the-art algorithms for artifact removal were inefficient for large datasets, as they require manual intervention. Thus, we introduced an EEG artifact removal algorithm with tuning parameters based on Wavelet Packet Decomposition (WPD). The proposed algorithm operates with two tuning parameters and three modes of wavelet filtering: Elimination, Linear Attenuation, and Soft-thresholding. Evaluating the algorithm performance, we observed that it outperforms state-of-the-art algorithms based on Independent Component Analysis (ICA). The evaluation was based on the spectrum, correlation, and distribution of the signals along with the performance in predictive tasks. We also demonstrate that a proper tuning of the algorithm parameters allows achieving further better results. After applying the artifact removal algorithm on EEG, we analysed the signals in terms of correlation of spectral bands of each electrode and attention score, semanticity, noise level, and state of the participant LWR). Next, we analyse the Event-Related Potential (ERP) on Listening, Writing and Resting segments of EEG signal, in addition to spectral analysis of GSR and PPG. With this thesis, we release the collected experimental dataset in the public domain, in order for the scientific community to further investigate the various auditory processing phenomena and their relation with EEG, GSR and PPG responses. The dataset can be used also to improve predictive tasks or design novel Brain-Computer-Interface (BCI) systems based on auditory attention. We also use the deeplearning approach to exploit the spatial relationship of EEG electrodes and inter-subject dependency of a model. As a domain application, we finally discuss the implications of auditory attention assessment for serious games and propose a 3-dimensional difficulty model to design game levels and dynamically adapt the difficulty to the player status