Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).

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Predicting Shifts in Land Suitability for Maize Cultivation Worldwide Due to Climate Change: A Modeling Approach

Land ◽

10.3390/land10030295 ◽

2021 ◽

Vol 10 (3) ◽

pp. 295

Author(s):

Yuan Gao ◽

Anyu Zhang ◽

Yaojie Yue ◽

Jing’ai Wang ◽

Peng Su

Keyword(s):

Climate Change ◽

Crop Production ◽

Large Scale ◽

Land Suitability ◽

Large Scale Assessment ◽

Scale Assessment ◽

Maize Cultivation ◽

Large Scale Screening ◽

Selection Of

Suitable land is an important prerequisite for crop cultivation and, given the prospect of climate change, it is essential to assess such suitability to minimize crop production risks and to ensure food security. Although a variety of methods to assess the suitability are available, a comprehensive, objective, and large-scale screening of environmental variables that influence the results—and therefore their accuracy—of these methods has rarely been explored. An approach to the selection of such variables is proposed and the criteria established for large-scale assessment of land, based on big data, for its suitability to maize (Zea mays L.) cultivation as a case study. The predicted suitability matched the past distribution of maize with an overall accuracy of 79% and a Kappa coefficient of 0.72. The land suitability for maize is likely to decrease markedly at low latitudes and even at mid latitudes. The total area suitable for maize globally and in most major maize-producing countries will decrease, the decrease being particularly steep in those regions optimally suited for maize at present. Compared with earlier research, the method proposed in the present paper is simple yet objective, comprehensive, and reliable for large-scale assessment. The findings of the study highlight the necessity of adopting relevant strategies to cope with the adverse impacts of climate change.

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Large Scale Screening Programme for Selection of Antisera for Radioimmunoassay of Human Parathyroid Hormone

Journal of Immunoassay ◽

10.1080/15321818308057009 ◽

1983 ◽

Vol 4 (2) ◽

pp. 175-206 ◽

Cited By ~ 8

Author(s):

Joan M. Zanelli ◽

B. Rafferty ◽

B. Apostolou ◽

G. Court ◽

B. A. L. Hurn

Keyword(s):

Parathyroid Hormone ◽

Large Scale ◽

Screening Programme ◽

Human Parathyroid Hormone ◽

Large Scale Screening ◽

Selection Of

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Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02582-16 ◽

2017 ◽

Vol 61 (5) ◽

Cited By ~ 104

Author(s):

Nuno Vale ◽

Maria João Gouveia ◽

Gabriel Rinaldi ◽

Paul J. Brindley ◽

Fátima Gärtner ◽

...

Keyword(s):

Rational Design ◽

Large Scale ◽

Sub Saharan Africa ◽

Screening Programs ◽

Drug Of Choice ◽

Sub Saharan ◽

New Compounds ◽

Derivatives Of ◽

Large Scale Screening ◽

Selection Of

ABSTRACT Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.

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Training Aides to Screen Children for Speech and Language Problems

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.0704.236 ◽

1976 ◽

Vol 7 (4) ◽

pp. 236-241 ◽

Cited By ~ 5

Author(s):

Marisue Pickering ◽

William R. Dopheide

Keyword(s):

Rural Areas ◽

Large Scale ◽

School Personnel ◽

School Age Children ◽

Speech And Language ◽

Elementary School Age ◽

Evaluation Procedures ◽

Language Problems ◽

Competency Based ◽

Large Scale Screening

This report deals with an effort to begin the process of effectively identifying children in rural areas with speech and language problems using existing school personnel. A two-day competency-based workshop for the purpose of training aides to conduct a large-scale screening of speech and language problems in elementary-school-age children is described. Training strategies, implementation, and evaluation procedures are discussed.

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Platelet Anti-Aggregating Activity and Tolerance of Clopidogrel in Atherosclerotic Patients

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650689 ◽

1996 ◽

Vol 76 (06) ◽

pp. 0939-0943 ◽

Cited By ~ 74

Author(s):

B Boneu ◽

G Destelle ◽

Keyword(s):

Platelet Aggregation ◽

Large Scale ◽

Bleeding Time ◽

Antithrombotic Activity ◽

Ambulatory Patients ◽

Patients At Risk ◽

Set Up ◽

Ischemic Events ◽

Large Scale Clinical Trial ◽

Selection Of

SummaryThe anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trial of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50,75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 \lM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.

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Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190122151634 ◽

2019 ◽

Vol 19 (1) ◽

pp. 4-16 ◽

Cited By ~ 6

Author(s):

Qihui Wu ◽

Hanzhong Ke ◽

Dongli Li ◽

Qi Wang ◽

Jiansong Fang ◽

...

Keyword(s):

Machine Learning ◽

Drug Discovery ◽

Large Scale ◽

Recent Progress ◽

High Specificity ◽

Learning Approaches ◽

Anticancer Peptides ◽

The Past ◽

Traditional Approaches ◽

Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

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Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening

Diagnostics ◽

10.3390/diagnostics11050869 ◽

2021 ◽

Vol 11 (5) ◽

pp. 869

Author(s):

Amedeo De Nicolò ◽

Valeria Avataneo ◽

Jessica Cusato ◽

Alice Palermiti ◽

Jacopo Mula ◽

...

Keyword(s):

Early Diagnosis ◽

Real Time Pcr ◽

Large Scale ◽

High Sensitivity ◽

Analytical Validation ◽

Pcr Assay ◽

Serological Tests ◽

Flow Test ◽

Lateral Flow Test ◽

Large Scale Screening

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.

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Methodology for Determining the Location of River Ports on a Modernized Waterway Based on Non-Cost Criteria: A Case Study of the Odra River Waterway

Sustainability ◽

10.3390/su13063571 ◽

2021 ◽

Vol 13 (6) ◽

pp. 3571

Author(s):

Bogusz Wiśnicki ◽

Dorota Dybkowska-Stefek ◽

Justyna Relisko-Rybak ◽

Łukasz Kolanda

Keyword(s):

Large Scale ◽

Multicriteria Decision Making ◽

Research Process ◽

Optimal Selection ◽

Investment Projects ◽

Odra River ◽

Research Problems ◽

Selection Of ◽

Construction Works

The paper responds to research problems related to the implementation of large-scale investment projects in waterways in Europe. As part of design and construction works, it is necessary to indicate river ports that play a major role within the European transport network as intermodal nodes. This entails a number of challenges, the cardinal one being the optimal selection of port locations, taking into account the new transport, economic, and geopolitical situation that will be brought about by modernized waterways. The aim of the paper was to present an original methodology for determining port locations for modernized waterways based on non-cost criteria, as an extended multicriteria decision-making method (MCDM) and employing GIS (Geographic Information System)-based tools for spatial analysis. The methodology was designed to be applicable to the varying conditions of a river’s hydroengineering structures (free-flowing river, canalized river, and canals) and adjustable to the requirements posed by intermodal supply chains. The method was applied to study the Odra River Waterway, which allowed the formulation of recommendations regarding the application of the method in the case of different river sections at every stage of the research process.

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Large-scale screening of natural genetic resource in the hydrocarbon-producing microalga Botrycoccus braunii identified novel fast-growing strains

Scientific Reports ◽

10.1038/s41598-021-86760-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Koji Kawamura ◽

Suzune Nishikawa ◽

Kotaro Hirano ◽

Ardianor Ardianor ◽

Rudy Agung Nugroho ◽

...

Keyword(s):

Large Scale ◽

Biomass Productivity ◽

Botryococcus Braunii ◽

Algal Biofuel ◽

Fast Growing ◽

Wild Strains ◽

Glass Tubes ◽

The Tropics ◽

Large Scale Screening ◽

Hydrocarbon Productivity

AbstractAlgal biofuel research aims to make a renewable, carbon–neutral biofuel by using oil-producing microalgae. The freshwater microalga Botryococcus braunii has received much attention due to its ability to accumulate large amounts of petroleum-like hydrocarbons but suffers from slow growth. We performed a large-scale screening of fast-growing strains with 180 strains isolated from 22 ponds located in a wide geographic range from the tropics to cool-temperate. A fast-growing strain, Showa, which recorded the highest productivities of algal hydrocarbons to date, was used as a benchmark. The initial screening was performed by monitoring optical densities in glass tubes and identified 9 wild strains with faster or equivalent growth rates to Showa. The biomass-based assessments showed that biomass and hydrocarbon productivities of these strains were 12–37% and 11–88% higher than that of Showa, respectively. One strain, OIT-678 established a new record of the fastest growth rate in the race B strains with a doubling time of 1.2 days. The OIT-678 had 36% higher biomass productivity, 34% higher hydrocarbon productivity, and 20% higher biomass density than Showa at the same cultivation conditions, suggesting the potential of the new strain to break the record for the highest productivities of hydrocarbons.

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