Generating hard-to-obtain information from easy-to-obtain information: Applications in drug discovery and clinical inference.
Ontology highlight
ABSTRACT:
SUBMITTER: Amodio M
PROVIDER: S-EPMC8276014 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In de novo drug design, computational strategies are used to generate novel molecules with good affinity to the desired biological target. In this work, we show that recurrent neural networks can be trained as generative models for molecular structures, similar to statistical language models in natural language processing. We demonstrate that the properties of the generated molecules correlate very well with the properties of the molecules used to train the model. In order to enrich libraries with molecules active toward a given biological target, we propose to fine-tune the model with small sets of molecules, which are known to be active against that target. Against Staphylococcus aureus, the model reproduced 14% of 6051 hold-out test molecules that medicinal chemists designed, whereas against Plasmodium falciparum (Malaria), it reproduced 28% of 1240 test molecules. When coupled with a scoring function, our model can perform the complete de novo drug design cycle to generate large sets of novel molecules for drug discovery.
| S-EPMC5785775 | biostudies-literature
Project description:A bibliometric analysis of PubChem applications is presented by reviewing 1132 research articles. The massive volume of chemical structure and bioactivity data in PubChem and its online services have been used globally in various fields including chemical biology, medicinal chemistry and informatics research. PubChem supports drug discovery in many aspects such as lead identification and optimization, compound-target profiling, polypharmacology studies and unknown chemical identity elucidation. PubChem has also become a valuable resource for developing secondary databases, informatics tools and web services. The growing PubChem resource with its public availability offers support and great opportunities for the interrogation of pharmacological mechanisms and the genetic basis of diseases, which are vital for drug innovation and repurposing.
| S-EPMC4252728 | biostudies-literature
Project description:MotivationOrthology inference constitutes a common base of many genome-based studies, as a pre-requisite for annotating new genomes, finding target genes for biotechnological applications and revealing the evolutionary history of life. Although its importance keeps rising with the ever-growing number of sequenced genomes, existing tools are computationally demanding and difficult to employ.ResultsHere, we present SonicParanoid, which is faster than, but comparably accurate to, the well-established tools with a balanced precision-recall trade-off. Furthermore, SonicParanoid substantially relieves the difficulties of orthology inference for those who need to construct and maintain their own genomic datasets.Availability and implementationSonicParanoid is available with a GNU GPLv3 license on the Python Package Index and BitBucket. Documentation is available at http://iwasakilab.bs.s.u-tokyo.ac.jp/sonicparanoid.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6298048 | biostudies-literature
Project description:BackgroundWith the rapid adoption of electronic health records (EHRs), it is desirable to harvest information and knowledge from EHRs to support automated systems at the point of care and to enable secondary use of EHRs for clinical and translational research. One critical component used to facilitate the secondary use of EHR data is the information extraction (IE) task, which automatically extracts and encodes clinical information from text.ObjectivesIn this literature review, we present a review of recent published research on clinical information extraction (IE) applications.MethodsA literature search was conducted for articles published from January 2009 to September 2016 based on Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and ACM Digital Library.ResultsA total of 1917 publications were identified for title and abstract screening. Of these publications, 263 articles were selected and discussed in this review in terms of publication venues and data sources, clinical IE tools, methods, and applications in the areas of disease- and drug-related studies, and clinical workflow optimizations.ConclusionsClinical IE has been used for a wide range of applications, however, there is a considerable gap between clinical studies using EHR data and studies using clinical IE. This study enabled us to gain a more concrete understanding of the gap and to provide potential solutions to bridge this gap.
| S-EPMC5771858 | biostudies-literature
Project description:The determination of the parameters of cylindrical optical waveguides, e.g. the diameters [Formula: see text] of r layers of (semi-) transparent optical fibres, can be executed by inverse evaluation of the scattering intensities that emerge under monochromatic illumination. The inverse problem can be solved by optimising the mismatch [Formula: see text] between the measured and simulated scattering patterns. The global optimum corresponds to the correct parameter values. The mismatch [Formula: see text] can be seen as an energy landscape as a function of the diameters. In this work, we study the structure of the energy landscape for different values of the complex refractive indices [Formula: see text], for [Formula: see text] and [Formula: see text] layers. We find that for both values of r, depending on the values of [Formula: see text], two very different types of energy landscapes exist, respectively. One type is dominated by one global minimum and the other type exhibits a multitude of local minima. From an algorithmic viewpoint, this corresponds to easy and hard phases, respectively. Our results indicate that the two phases are separated by sharp phase-transition lines and that the shape of these lines can be described by one "critical" exponent b, which depends slightly on r. Interestingly, the same exponent also describes the dependence of the number of local minima on the diameters. Thus, our findings are comparable to previous theoretical studies on easy-hard transitions in basic combinatorial optimisation or decision problems like Travelling Salesperson and Satisfiability. To our knowledge our results are the first indicating the existence of easy-hard transitions for a real-world optimisation problem of technological relevance.
| S-EPMC7562953 | biostudies-literature
Project description:Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.
| S-EPMC9986049 | biostudies-literature
Project description:Computer simulation techniques are gaining a central role in molecular pharmacology. Due to several factors, including the significant improvements of traditional molecular modelling, the irruption of machine learning methods, the massive data generation, or the unlimited computational resources through cloud computing, the future of pharmacology seems to go hand in hand with in silico predictions. In this review, we summarize our recent efforts in such a direction, centered on the unconventional Monte Carlo PELE software and on its coupling with machine learning techniques. We also provide new data on combining two recent new techniques, aquaPELE capable of exhaustive water sampling and fragPELE, for fragment growing.
| S-EPMC9788188 | biostudies-literature
Project description:Interest in exploiting allosteric sites for the development of new therapeutics has grown considerably over the last two decades. The chief driving force behind the interest in allostery for drug discovery stems from the fact that in comparison to orthosteric sites, allosteric sites are less conserved across a protein family, thereby offering greater opportunity for selectivity and ultimately tolerability. While there is significant overlap between structure-based drug design for orthosteric and allosteric sites, allosteric sites offer additional challenges mostly involving the need to better understand protein flexibility and its relationship to protein function. Here we examine the extent to which structure-based drug design is impacting allosteric drug design by highlighting several targets across a variety of target classes.
| S-EPMC9877542 | biostudies-literature
Project description:Conventional wet laboratory testing, validations, and synthetic procedures are costly and time-consuming for drug discovery. Advancements in artificial intelligence (AI) techniques have revolutionized their applications to drug discovery. Combined with accessible data resources, AI techniques are changing the landscape of drug discovery. In the past decades, a series of AI-based models have been developed for various steps of drug discovery. These models have been used as complements of conventional experiments and have accelerated the drug discovery process. In this review, we first introduced the widely used data resources in drug discovery, such as ChEMBL and DrugBank, followed by the molecular representation schemes that convert data into computer-readable formats. Meanwhile, we summarized the algorithms used to develop AI-based models for drug discovery. Subsequently, we discussed the applications of AI techniques in pharmaceutical analysis including predicting drug toxicity, drug bioactivity, and drug physicochemical property. Furthermore, we introduced the AI-based models for de novo drug design, drug-target structure prediction, drug-target interaction, and binding affinity prediction. Moreover, we also highlighted the advanced applications of AI in drug synergism/antagonism prediction and nanomedicine design. Finally, we discussed the challenges and future perspectives on the applications of AI to drug discovery.
| S-EPMC10009646 | biostudies-literature
Project description:Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediting the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.
| S-EPMC1978280 | biostudies-other