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An incomplete understanding of the technical details in a firm's technology selection can lead to a failure in the process of the technology opportunity discovery (TOD) and cause a series of R&D problems. This study proposes an approach for the automated TOD by combining the subject-section-object (SAO) and the generative topographic mapping (GTM), which concentrates on the role of the semantic information in TOD process. First, the semantic information of the technology components in a target field is extracted and the topics of different semantic structures are defined. Second, the GTM-based patent map is established to discover technology opportunities based on a vector matrix composed of patents and topics. Finally, the degree of semantic similarity is applied to measure the technology novelty and to identify promising technology opportunities. The case of the coal-bed methane extraction technology demonstrates that the automated approach based on the semantic information can help understand the concrete details of technology opportunities and improve the accuracy of TOD. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicles equipped with hyperspectral imagers have emerged as an essential technology for the characterization of inland water bodies. The high spectral and spatial resolutions of these systems enable the retrieval of a plethora of optically active water quality parameters via band ratio algorithms and machine learning methods. However, fitting and validating these models requires access to sufficient quantities of in situ reference data which are time-consuming and expensive to obtain. In this study, we demonstrate how Generative Topographic Mapping (GTM), a probabilistic realization of the self-organizing map, can be used to visualize high-dimensional hyperspectral imagery and extract spectral signatures corresponding to unique endmembers present in the water. Using data collected across a North Texas pond, we first apply GTM to visualize the distribution of captured reflectance spectra, revealing the small-scale spatial variability of the water composition. Next, we demonstrate how the nodes of the fitted GTM can be interpreted as unique spectral endmembers. Using extracted endmembers together with the normalized spectral similarity score, we are able to efficiently map the abundance of nearshore algae, as well as the evolution of a rhodamine tracer dye used to simulate water contamination by a localized source. [ABSTRACT FROM AUTHOR]

Increasing antimicrobial resistance (AMR) represents a global healthcare threat. To decrease the spread of AMR and associated mortality, methods for rapid selection of optimal antibiotic treatment are urgently needed. Machine learning (ML) models based on genomic data to predict resistant phenotypes can serve as a fast screening tool prior to phenotypic testing. Nonetheless, many existing ML methods lack interpretability. Therefore, we present a methodology for visualization of sequence space and AMR prediction based on the non‐linear dimensionality reduction method – generative topographic mapping (GTM). This approach, applied to AMR data of >5000 S. aureus isolates retrieved from the PATRIC database, yielded GTM models with reasonable accuracy for all drugs (balanced accuracy values ≥0.75). The Generative Topographic Maps (GTMs) represent data in the form of illustrative maps of the genomic space and allow for antibiotic‐wise comparison of resistant phenotypes. The maps were also found to be useful for the analysis of genetic determinants responsible for drug resistance. Overall, the GTM‐based methodology is a useful tool for both the illustrative exploration of the genomic sequence space and AMR prediction. [ABSTRACT FROM AUTHOR]

Summary: Background: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. Methods: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward’s minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. Findings: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. Interpretation: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. Funding: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).

Abstract Freedom of expression is a core human right, yet the forces that seek to suppress it have intensified, increasing the need to develop tools that can measure the rates of freedom globally. In this study, we propose a novel freedom of expression index to gain a nuanced and data-led understanding of the level of censorship across the globe. For this, we used an unsupervised, probabilistic machine learning method, to model the status of the free expression landscape. This index seeks to provide legislators and other policymakers, activists and governments, and non-governmental and intergovernmental organisations, with tools to better inform policy or action decisions. The global nature of the proposed index also means it can become a vital resource/tool for engagement with international and supranational bodies.

Unmanned aerial vehicles equipped with hyperspectral imagers have emerged as an essential technology for the characterization of inland water bodies. The high spectral and spatial resolutions of these systems enable the retrieval of a plethora of optically active water quality parameters via band ratio algorithms and machine learning methods. However, fitting and validating these models requires access to sufficient quantities of in situ reference data which are time-consuming and expensive to obtain. In this study, we demonstrate how Generative Topographic Mapping (GTM), a probabilistic realization of the self-organizing map, can be used to visualize high-dimensional hyperspectral imagery and extract spectral signatures corresponding to unique endmembers present in the water. Using data collected across a North Texas pond, we first apply GTM to visualize the distribution of captured reflectance spectra, revealing the small-scale spatial variability of the water composition. Next, we demonstrate how the nodes of the fitted GTM can be interpreted as unique spectral endmembers. Using extracted endmembers together with the normalized spectral similarity score, we are able to efficiently map the abundance of nearshore algae, as well as the evolution of a rhodamine tracer dye used to simulate water contamination by a localized source.

Freedom of expression is a core human right, yet the forces that seek to suppress it have intensified, increasing the need to develop tools that can measure the rates of freedom globally. In this study, we propose a novel freedom of expression index to gain a nuanced and data-led understanding of the level of censorship across the globe. For this, we used an unsupervised, probabilistic machine learning method, to model the status of the free expression landscape. This index seeks to provide legislators and other policymakers, activists and governments, and non-governmental and intergovernmental organisations, with tools to better inform policy or action decisions. The global nature of the proposed index also means it can become a vital resource/tool for engagement with international and supranational bodies.Article highlights: We propose a novel methodology using machine learning to model freedom of expression on a global scale. The proposed approach is in nature less prone to subjective interpretation and possibly more rigorous than previous rankings. The resulting freedom of expression indices can be used as a powerful tool to better inform policy or action decisions. [ABSTRACT FROM AUTHOR]

In order to analyze the Chimiothèque Nationale (CN) – The French National Compound Library – in the context of screening and biologically relevant compounds, the library was compared with ZINC in‐stock collection and ChEMBL. This includes the study of chemical space coverage, physicochemical properties and Bemis‐Murcko (BM) scaffold populations. More than 5 K CN‐unique scaffolds (relative to ZINC and ChEMBL collections) were identified. Generative Topographic Maps (GTMs) accommodating those libraries were generated and used to compare the compound populations. Hierarchical GTM («zooming») was applied to generate an ensemble of maps at various resolution levels, from global overview to precise mapping of individual structures. The respective maps were added to the ChemSpace Atlas website. The analysis of synthetic accessibility in the context of combinatorial chemistry showed that only 29,7 % of CN compounds can be fully synthesized using commercially available building blocks. [ABSTRACT FROM AUTHOR]

Information about the species composition of a forest is necessary for assessing biodiversity in a particular region and making economic decisions on the management of forest resources. Recognition of the species composition, according to the Earth's remote sensing data, greatly simplifies the work and reduces time and labor costs in comparison with a traditional inventory of the forest, conducted through ground-based observations. This study analyzes the possibilities of tree species discrimination in coniferous–deciduous forests according to Sentinel-2 data using two automated recognition methods: random forest (RF) and generative topographic mapping (GTM). As remote sensing data, Sentinel-2 images of the Raifa section of Volga-Kama State Reserve in the Tatarstan Republic, Russia used: six images for the vegetation period of 2020. The analysis was carried out for the main forest-forming species. The training sample was created based on the cadastral data of the forest fund. The recognition quality was assessed using the F1-score, precision, recall, and accuracy metrics. The RF method showed a higher recognition accuracy. The accuracy of correct recognition by the RF method on the training sample reaches 0.987, F1-score = 0.976, on the control sample, accuracy = 0.764, F1-score = 0.709. [ABSTRACT FROM AUTHOR]

Dimensionality reduction is an important exploratory data analysis method that allows high-dimensional data to be represented in a human-interpretable lower-dimensional space. It is extensively applied in the analysis of chemical libraries, where chemical structure data - represented as high-dimensional feature vectors-are transformed into 2D or 3D chemical space maps. In this paper, commonly used dimensionality reduction techniques - Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), Uniform Manifold Approximation and Projection (UMAP), and Generative Topographic Mapping (GTM) - are evaluated in terms of neighborhood preservation and visualization capability of sets of small molecules from the ChEMBL database., (© 2024 The Author(s). Molecular Informatics published by Wiley-VCH GmbH.)

Topological data analysis tools enjoy increasing popularity in a wide range of applications, such as Computer graphics, Image analysis, Machine learning, and Astronomy for extracting information. However, due to computational complexity, processing large numbers of samples of higher dimensionality quickly becomes infeasible. This contribution is twofold: We present an efficient novel sub-sampling strategy inspired by Coulomb's law to decrease the number of data points in d -dimensional point clouds while preserving its homology. The method is not only capable of reducing the memory and computation time needed for the construction of different types of simplicial complexes but also preserves the size of the voids in d -dimensions, which is crucial e.g. for astronomical applications. Furthermore, we propose a technique to construct a probabilistic description of the border of significant cycles and cavities inside the point cloud. We demonstrate and empirically compare the strategy in several synthetic scenarios and an astronomical particle simulation of a dwarf galaxy for the detection of superbubbles (supernova signatures). [ABSTRACT FROM AUTHOR]

Information about the species composition of a forest is necessary for assessing biodiversity in a particular region and making economic decisions on the management of forest resources. Recognition of the species composition, according to the Earth’s remote sensing data, greatly simplifies the work and reduces time and labor costs in comparison with a traditional inventory of the forest, conducted through ground-based observations. This study analyzes the possibilities of tree species discrimination in coniferous–deciduous forests according to Sentinel-2 data using two automated recognition methods: random forest (RF) and generative topographic mapping (GTM). As remote sensing data, Sentinel-2 images of the Raifa section of Volga-Kama State Reserve in the Tatarstan Republic, Russia used: six images for the vegetation period of 2020. The analysis was carried out for the main forest-forming species. The training sample was created based on the cadastral data of the forest fund. The recognition quality was assessed using the F1-score, precision, recall, and accuracy metrics. The RF method showed a higher recognition accuracy. The accuracy of correct recognition by the RF method on the training sample reaches 0.987, F1-score = 0.976, on the control sample, accuracy = 0.764, F1-score = 0.709.

Background: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations., Methods: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward's minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations., Findings: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations., Interpretation: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions., Funding: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624)., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The advent of high-performance virtual screening techniques nowadays allows drug designers to explore ultra-large sets of candidate compounds in search of molecules predicted to have desired properties. However, the success of such an endeavor heavily relies on the pertinence (drug-likeness and, foremost, chemical feasibility) of these candidates, or otherwise, virtual screening will return valueless "hits", by the garbage in/garbage out principle. The huge popularity of the judiciously enumerated Enamine REAL Space is clear proof of the strength of this Big Data trend in drug discovery. Here we describe a new dataset of make-on-demand compounds called the Freedom space. It follows the principles of Enamine REAL Space and contains highly feasible molecules (synthesis success rate over 75 percent). However, the scaffold and chemography analysis revealed significant differences to both the REAL and biologically annotated compounds from the ChEMBL database. The Freedom Space is a significant extension of the REAL Space and can be utilized for a more comprehensive exploration of the synthetically feasible chemical space in hit finding and hit-to-lead campaigns., (© 2024 Wiley-VCH GmbH.)

Visualization and analysis of large chemical reaction networks become rather challenging when conventional graph-based approaches are used. As an alternative, we propose to use the chemical cartography ("chemography") approach, describing the data distribution on a 2-dimensional map. Here, the Generative Topographic Mapping (GTM) algorithm - an advanced chemography approach - has been applied to visualize the reaction path network of a simplified Wilkinson's catalyst-catalyzed hydrogenation containing some 10 5 structures generated with the help of the Artificial Force Induced Reaction (AFIR) method using either Density Functional Theory or Neural Network Potential (NNP) for potential energy surface calculations. Using new atoms permutation invariant 3D descriptors for structure encoding, we've demonstrated that GTM possesses the abilities to cluster structures that share the same 2D representation, to visualize potential energy surface, to provide an insight on the reaction path exploration as a function of time and to compare reaction path networks obtained with different methods of energy assessment., (© 2024 Wiley-VCH GmbH.)

Abstract Background Principal component analysis (PCA) is a standard method to correct for population stratification in ancestry-specific genome-wide association studies (GWASs) and is used to cluster individuals by ancestry. Using the 1000 genomes project data, we examine how non-linear dimensionality reduction methods such as t-distributed stochastic neighbor embedding (t-SNE) or generative topographic mapping (GTM) can be used to provide improved ancestry maps by accounting for a higher percentage of explained variance in ancestry, and how they can help to estimate the number of principal components necessary to account for population stratification. GTM generates posterior probabilities of class membership which can be used to assess the probability of an individual to belong to a given population - as opposed to t-SNE, GTM can be used for both clustering and classification. Results PCA only partially identifies population clusters and does not separate most populations within a given continent, such as Japanese and Han Chinese in East Asia, or Mende and Yoruba in Africa. t-SNE and GTM, taking into account more data variance, can identify more fine-grained population clusters. GTM can be used to build probabilistic classification models, and is as efficient as support vector machine (SVM) for classifying 1000 Genomes Project populations. Conclusion The main interest of probabilistic GTM maps is to attain two objectives with only one map: provide a better visualization that separates populations efficiently, and infer genetic ancestry for individuals or populations. This paper is a first application of GTM for ancestry classification models. Our code (https://github.com/hagax8/ancestry_viz) and interactive visualizations (https://lovingscience.com/ancestries) are available online.

This paper is devoted to the analysis of available experimental data and preparation of predictive models for binding affinity of molecules with respect to two nuclear receptors involved in endocrine disruption (ED): the oestrogen (ER) and the androgen (AR) receptors. The ED-relevant data were retrieved from multiple sources, including the CERAPP, CoMPARA, and the Tox21 projects as well as ChEMBL and PubChem databases. Data analysis performed with the help of generative topographic mapping revealed the problem of low agreement between experimental values from different sources. Collected data were used to train both classification models for ER and AR binding activities and regression models for relative binding affinity (RBA) and median inhibition concentration (IC50). These models displayed relatively poor performance in classification (sensitivities ER = 0.34, AR = 0.49) and in regression (determination coefficient r2 for the RBA and IC50 models in external validation varied from 0.44 to 0.76). Our analysis demonstrates that low models' performance resulted from misinterpreted experimental endpoints or wrongly reported values, thus confirming the observations reported in CERAPP and CoMPARA studies. Developed models and collected data sets included of 6215 (ER) and 3789 (AR) unique compounds, which are freely available. [ABSTRACT FROM AUTHOR]

Discovery of drugs against newly emerged pathogenic agents like the SARS‐CoV‐2 coronavirus (CoV) must be based on previous research against related species. Scientists need to get acquainted with and develop a global oversight over so‐far tested molecules. Chemography (herein used Generative Topographic Mapping, in particular) places structures on a human‐readable 2D map (obtained by dimensionality reduction of the chemical space of molecular descriptors) and is thus well suited for such an audit. The goal is to map medicinal chemistry efforts so far targeted against CoVs. This includes comparing libraries tested against various virus species/genera, predicting their polypharmacological profiles and highlighting often encountered chemotypes. Maps are challenged to provide predictive activity landscapes against viral proteins. Definition of "anti‐CoV" map zones led to selection of therein residing 380 potential anti‐CoV agents, out of a vast pool of 800 M organic compounds. [ABSTRACT FROM AUTHOR]

The flock structures produced by individuals, e.g., animals, self-organize and change their complexity over time. Although flock structures are often characterized by the spatial alignment of each element, this study focuses on their dynamic and hierarchical nature, temporal variations, and meta-structures. In hierarchical systems, sometimes, the upper structure is unchanged, whereas the lower components change constantly over time. Current clustering methods aim to capture the static and mono-layer features of complex patterning. To detect and track dynamic and hierarchical objects, a new clustering technique is required. Hence, in this study, we improve the generative topographic mapping (GTM) method to visualize such dynamic hierarchical structures as they continuously change over time. Using examples from our recent studies on the large-scale Boids model, we confirm that the newly developed method can capture the complex flocking objects as well as track the merging and collapsing events of objects. [ABSTRACT FROM AUTHOR]

Here we report a new predictive model for autoignition temperature (AIT), an important physical parameter widely used to assess potential safety hazards of combustible materials. Available structure-AIT data extracted from different sources were critically analysed. Support vector regression (SVR) models on different data subsets were built in order to identify a reliable compound set on which a realistic model could be built. This led to a selection of the dataset containing 875 compounds annotated with AIT values. The thereupon-based SVR model performs reasonably well in cross-validation with the determination coefficient r2 = 0.77 and mean absolute error MAE = 37.8°C. External validation on 20 industrial compounds missing in the training set confirmed its good predictive power (MAE = 28.7°C). [ABSTRACT FROM AUTHOR]

Generative topographic mapping was used to investigate the possibility to diversify the in-house compounds collection of Boehringer Ingelheim (BI). For this purpose, a 2D map covering the relevant chemical space was trained, and the BI compound library was compared to the Aldrich-Market Select (AMS) database of more than 8M purchasable compounds. In order to discover new (sub)structures, the "AutoZoom" tool was developed and applied in order to analyze chemotypes of molecules residing in heavily populated zones of a map and to extract the corresponding maximum common substructures. A set of 401K new structures from the AMS database was retrieved and checked for drug-likeness and biological activity. [ABSTRACT FROM AUTHOR]

Generative Topographic Mapping (GTM) is a dimensionality reduction method, which is widely used for both data visualization and structure‐activity modeling. Large dimensionality of the initial data space may require significant computational resources and slow down the GTM construction. Therefore, it may be meaningful to reduce the number of descriptors used for encoding molecular structures. The Principal Component Analysis (PCA), a standard preprocessing tool, suffers from the information loss upon the dimensionality reduction. As an alternative, we propose to use substructure vector embedding provided by the mol2vec technique. In addition to the data dimensionality reduction, this technology also accounts for proximity of substructures in molecular graphs. In this study, dimensionality of large descriptor spaces of ISIDA fragment descriptors or Morgan fingerprints were reduced using either the PCA or the mol2vec method. The latter significantly speeds up GTM training without compromising its predictive power in bioactivity classification tasks. [ABSTRACT FROM AUTHOR]

Prediction of molecular properties plays a critical role towards rational drug design. In this study, the Molecular Topographic Map (MTM) is proposed, which is a two-dimensional (2D) map that can be used to represent a molecule. An MTM is generated from the atomic features set of a molecule using generative topographic mapping and is then used as input data for analyzing structure-property/activity relationships. In the visualization and classification of 20 amino acids, differences of the amino acids can be visually confirmed from and revealed by hierarchical clustering with a similarity matrix of their MTMs. The prediction of molecular properties was performed on the basis of convolutional neural networks using MTMs as input data. The performance of the predictive models using MTM was found to be equal to or better than that using Morgan fingerprint or MACCS keys. Furthermore, data augmentation of MTMs using mixup has improved the prediction performance. Since molecules converted to MTMs can be treated like 2D images, they can be easily used with existing neural networks for image recognition and related technologies. MTM can be effectively utilized to predict molecular properties of small molecules to aid drug discovery research.

Functioning of rotary machines is based on the rolling element of bearings, as the rolling element of bearings is the crucial component of rotary machines. The entire operation of rotating machines may terminate after the failure of rolling element of bearings. Hence, the failure of rotating machine is mainly dependent on rolling element of bearings, as it may break down an entire process. Thus, to avoid the sudden breakdown of rotary machines, it is essential to develop the diagnostics and prognostics methodology of rolling element of bearings. In the rolling element of bearings, the assessment of bearing degradation and fault diagnostics is essential to establish the methodology. Therefore, this article proposes a methodology to diagnose the fault of bearing and to assess bearing degradation. Envelope spectra and generative topographic mapping are used together in the methodology proposed. Selection of frequency band based on encompasses one or more resonance of spectrum of signal. Envelope spectrum is determined to pick up the peak of the characteristic fault frequencies of the bearing. Extraction of features from time and frequency domains is used in the generative topographic mapping. Health degradation index, an index termed as evolution of bearing degradation, is obtained from the classifier of generative topographic mapping. Experiments were conducted on the bearings to verify the proposed methodology. On interpreting the obtained results, it was found that the proficiency of proposed methodology is most appropriate for detecting the fault in bearing and tracking the degradation evolution in bearings. [ABSTRACT FROM AUTHOR]

Background: Principal component analysis (PCA) is a standard method to correct for population stratification in ancestry-specific genome-wide association studies (GWASs) and is used to cluster individuals by ancestry. Using the 1000 genomes project data, we examine how non-linear dimensionality reduction methods such as t-distributed stochastic neighbor embedding (t-SNE) or generative topographic mapping (GTM) can be used to provide improved ancestry maps by accounting for a higher percentage of explained variance in ancestry, and how they can help to estimate the number of principal components necessary to account for population stratification. GTM generates posterior probabilities of class membership which can be used to assess the probability of an individual to belong to a given population - as opposed to t-SNE, GTM can be used for both clustering and classification. Results: PCA only partially identifies population clusters and does not separate most populations within a given continent, such as Japanese and Han Chinese in East Asia, or Mende and Yoruba in Africa. t-SNE and GTM, taking into account more data variance, can identify more fine-grained population clusters. GTM can be used to build probabilistic classification models, and is as efficient as support vector machine (SVM) for classifying 1000 Genomes Project populations. Conclusion: The main interest of probabilistic GTM maps is to attain two objectives with only one map: provide a better visualization that separates populations efficiently, and infer genetic ancestry for individuals or populations. This paper is a first application of GTM for ancestry classification models. Our code (https://github.com/hagax8/ancestry%5fviz) and interactive visualizations (https://lovingscience.com/ancestries) are available online. [ABSTRACT FROM AUTHOR]

The previously reported procedure to generate "universal" Generative Topographic Maps (GTMs) of the drug-like chemical space is in practice a multi-task learning process, in which both operational GTM parameters (example: map grid size) and hyperparameters (key example: the molecular descriptor space to be used) are being chosen by an evolutionary process in order to fit/select "universal" GTM manifolds. After selection (a one-time task aimed at optimizing the compromise in terms of neighborhood behavior compliance, over a large pool of various biological targets), for any further use the manifolds are ready to provide "fit-free" predictive models. Using any structure-activity set—irrespectively whether the associated target served at map fitting stage or not—the generation or "coloring" a property landscape enables predicting the property for any external molecule, with zero additional fitable parameters involved. While previous works have signaled the excellent behavior of such models in aggressive three-fold cross-validation assessments of their predictive power, the present work wished to explore their behavior in Virtual Screening (VS), here simulated on hand of external DUD ligand and decoy series that are fully disjoint from the ChEMBL-extracted landscape coloring sets. Beyond the rather robust results of the universal GTM manifolds in this challenge, it could be shown that the descriptor spaces selected by the evolutionary multi-task learner were intrinsically able to serve as an excellent support for many other VS procedures, starting from parameter-free similarity searching, to local (target-specific) GTM models, to parameter-rich, nonlinear Random Forest and Neural Network approaches. [ABSTRACT FROM AUTHOR]

Abstract The Virtual Screening (VS) study described herein aimed at detecting novel Bromodomain BRD4 binders and relied on knowledge from public databases (ChEMBL, REAXYS) to establish a battery of predictive models of BRD activity for in silico selection of putative ligands. Beyond the actual discovery of new BRD ligands, this represented an opportunity to practically estimate the actual usefulness of public domain "Big Data" for robust predictive model building. Obtained models were used to virtually screen a collection of 2 million compounds from the Enamine company collection. This industrial partner then experimentally screened a subset of 2992 molecules selected by the VS procedure for their high likelihood to be active. Twenty nine confirmed hits were detected after experimental testing, representing 1% of the selected candidates. As a general conclusion, this study emphasizes once more that public structure-activity databases are nowadays key assets in drug discovery. Their usefulness is however limited by the state-of-the-art knowledge harvested so far by published studies. Target-specific structure-activity information is rarely rich enough, and its heterogeneity makes it extremely difficult to exploit in rational drug design. Furthermore, published affinity measures serving to build models selecting compounds to be experimentally screened may not be well correlated with the experimental hit selection criterion (in practice, often imposed by equipment constraints). Nevertheless, a robust 2.6-fold increase in hit rate with respect to an equivalent, random screening campaign showed that machine learning is able to extract some real knowledge in spite of all the noise in structure-activity data. Graphical abstract Image 1 Highlights • VS for bromodomain inhibitors utilizes public data sources, assessing their quality. • Rigorous experimental benchmark against random screening under identical conditions. • Virtual hits selected from consensus of GTM (mapping), machine learning, docking. • 29 hits were confirmed, i.e. 2.6 times more than in equivalent random screening. • Heterogeneity of public data and in-house measures negatively impacts enrichment. [ABSTRACT FROM AUTHOR]

ugtm is a Python package that implements generative topographic mapping (GTM), a dimensionality reduction algorithm by Bishop, Svensén and Williams. Because of its probabilistic framework, GTM can also be used to build classification and regression models, and is an attractive alternative to t-distributed neighbour embedding (t-SNE) or other non-linear dimensionality reduction methods. The package is compatible with scikit-learn, and includes a GTM transformer (eGTM), a GTM classifier (eGTC) and a GTM regressor (eGTR). The input and output of these functions are numpy arrays. The package implements supplementary functions for GTM visualization and kernel GTM (kGTM). The code is under MIT license and available on GitHub (https://github.com/hagax8/ugtm). For installation instructions and documentation, cf. https://ugtm.readthedocs.io. Funding statement: HG acknowledges funding from the US National Institute of Mental Health (PGC3: U01 MH109528).

Abstract: Generative Topographic Mapping (GTM) approach was successfully used to visualize, analyze and model the equilibrium constants (KT) of tautomeric transformations as a function of both structure and experimental conditions. The modeling set contained 695 entries corresponding to 350 unique transformations of 10 tautomeric types, for which KT values were measured in different solvents and at different temperatures. Two types of GTM‐based classification models were trained: first, a “structural” approach focused on separating tautomeric classes, irrespective of reaction conditions, then a “general” approach accounting for both structure and conditions. In both cases, the cross‐validated Balanced Accuracy was close to 1 and the clusters, assembling equilibria of particular classes, were well separated in 2‐dimentional GTM latent space. Data points corresponding to similar transformations measured under different experimental conditions, are well separated on the maps. Additionally, GTM‐driven regression models were found to have their predictive performance dependent on different scenarios of the selection of local fragment descriptors involving special marked atoms (proton donors or acceptors). The application of local descriptors significantly improves the model performance in 5‐fold cross‐validation: RMSE=0.63 and 0.82 logKT units with and without local descriptors, respectively. This trend was as well observed for SVR calculations, performed for the comparison purposes. [ABSTRACT FROM AUTHOR]

Technology opportunity analysis (TOA) with ideas generation has been recognized an important activity to remain competitive and lead the industry in the future. However, there are several issues with existing TOA, such as an unclear path from technology opportunities to ideas generation, a fuzzy integration between automated TOA techniques and expert-based methods, and a lack of detailed schemes for technology opportunities. This study proposes a new systematic approach to show the way from technology opportunities to ideas generation via cross-cutting patent analysis. The proposed approach is comprised of three stages: 1) establishing a cross-cutting relationship between the target and reference technologies through the results of F-terms; 2) collecting and processing patents to construct patent-keyword vector matrices of the target and reference technologies, respectively; and 3) migrating corresponding ideas via cosine similarity and link prediction for the target technology opportunities that are discovered based on generative topographic mapping (GTM). The feasibility and effectiveness of the proposed approach is demonstrated by empirical research on the exploitation technology in both the natural gas hydrate (NGH) and the coal bed methane (CBM) fields. This study represents a contribution to expand the existing TOA research into generating creative ideas by providing more detailed schemes for technology opportunities. • A systematic approach from technology opportunities to ideas generation is provided. • Our approach employs generative topographic mapping and link prediction. • Generative topographic mapping is used to identify target technology opportunities. • Link prediction is used to generate ideas from the reference technology via cross-cutting patent analysis. [ABSTRACT FROM AUTHOR]