Large-Scale Systematic Analysis of 2D Fingerprint Methods and Parameters to Improve Virtual Screening Enrichments

2010 ◽  
Vol 50 (5) ◽  
pp. 771-784 ◽  
Author(s):  
Madhavi Sastry ◽  
Jeffrey F. Lowrie ◽  
Steven L. Dixon ◽  
Woody Sherman
Keyword(s):  
Virtual Screening ◽  
Large Scale ◽  
Systematic Analysis

scholarly journals A novel ligand of the translationally controlled tumor protein (TCTP) identified by virtual drug screening for cancer differentiation therapy

2021 ◽  
Author(s):  
Nicolas Fischer ◽  
Ean-Jeong Seo ◽  
Sara Abdelfatah ◽  
Edmond Fleischer ◽  
Anette Klinger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Virtual Screening ◽  
Small Molecules ◽  
Large Scale ◽  
Differentiation Therapy ◽  
P53 Expression ◽  
Microscale Thermophoresis ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Mcf 7

SummaryIntroduction Differentiation therapy is a promising strategy for cancer treatment. The translationally controlled tumor protein (TCTP) is an encouraging target in this context. By now, this field of research is still at its infancy, which motivated us to perform a large-scale screening for the identification of novel ligands of TCTP. We studied the binding mode and the effect of TCTP blockade on the cell cycle in different cancer cell lines. Methods Based on the ZINC-database, we performed virtual screening of 2,556,750 compounds to analyze the binding of small molecules to TCTP. The in silico results were confirmed by microscale thermophoresis. The effect of the new ligand molecules was investigated on cancer cell survival, flow cytometric cell cycle analysis and protein expression by Western blotting and co-immunoprecipitation in MOLT-4, MDA-MB-231, SK-OV-3 and MCF-7 cells. Results Large-scale virtual screening by PyRx combined with molecular docking by AutoDock4 revealed five candidate compounds. By microscale thermophoresis, ZINC10157406 (6-(4-fluorophenyl)-2-[(8-methoxy-4-methyl-2-quinazolinyl)amino]-4(3H)-pyrimidinone) was identified as TCTP ligand with a KD of 0.87 ± 0.38. ZINC10157406 revealed growth inhibitory effects and caused G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. ZINC10157406 (2 × IC50) downregulated TCTP expression by 86.70 ± 0.44% and upregulated p53 expression by 177.60 ± 12.46%. We validated ZINC10157406 binding to the p53 interaction site of TCTP and replacing p53 by co-immunoprecipitation. Discussion ZINC10157406 was identified as potent ligand of TCTP by in silico and in vitro methods. The compound bound to TCTP with a considerably higher affinity compared to artesunate as known TCTP inhibitor. We were able to demonstrate the effect of TCTP blockade at the p53 binding site, i.e. expression of TCTP decreased, whereas p53 expression increased. This effect was accompanied by a dose-dependent decrease of CDK2, CDK4, CDK, cyclin D1 and cyclin D3 causing a G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. Our findings are supposed to stimulate further research on TCTP-specific small molecules for differentiation therapy in oncology.

DISAST-CIR: Disastrous Incidents Systematic Analysis Through Components, Interactions and Results: Application to a Large-Scale Train Accident

2009 ◽  
Vol 37 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Adi Leiba ◽  
Dagan Schwartz ◽  
Talor Eran ◽  
Amir Blumenfeld ◽  
Daniel Laor ◽  
...  
Keyword(s):  
Large Scale ◽  
Systematic Analysis

scholarly journals A Systematic Analysis of Big Image Data Methodologies in Various Applications

2020 ◽  
Vol 9 (5) ◽  
pp. 483-487
Keyword(s):  
Big Data ◽  
Deep Learning ◽  
Large Scale ◽  
Image Data ◽  
Computational Time ◽  
Process Data ◽  
Systematic Analysis ◽  
Large Scale Data ◽  
Learning Techniques ◽  
Effective Performance

Big data is large-scale data collected for knowledge discovery, it has been widely used in various applications. Big data often has image data from the various applications and requires effective technique to process data. In this paper, survey has been done in the big image data researches to analysis the effective performance of the methods. Deep learning techniques provides the effective performance compared to other methods included wavelet based methods. The deep learning techniques has the problem of requiring more computational time, and this can be overcome by lightweight methods.

scholarly journals Systematic analysis of copy number variation associated with congenital diaphragmatic hernia

2018 ◽  
Vol 115 (20) ◽  
pp. 5247-5252 ◽  
Author(s):  
Qihui Zhu ◽  
Frances A. High ◽  
Chengsheng Zhang ◽  
Eliza Cerveira ◽  
Meaghan K. Russell ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Candidate Genes ◽  
Birth Defects ◽  
Diaphragmatic Hernia ◽  
Copy Number ◽  
Large Scale ◽  
De Novo ◽  
Comparative Genomic ◽  
High Morbidity ◽  
Systematic Analysis

Congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and hypoplasia of the lungs, is one of the most common and severe birth defects, and is associated with high morbidity and mortality rates. There is growing evidence demonstrating that genetic factors contribute to CDH, although the pathogenesis remains largely elusive. Single-nucleotide polymorphisms have been studied in recent whole-exome sequencing efforts, but larger copy number variants (CNVs) have not yet been studied on a large scale in a case control study. To capture CNVs within CDH candidate regions, we developed and tested a targeted array comparative genomic hybridization platform to identify CNVs within 140 regions in 196 patients and 987 healthy controls, and identified six significant CNVs that were either unique to patients or enriched in patients compared with controls. These CDH-associated CNVs reveal high-priority candidate genes including HLX, LHX1, and HNF1B. We also discuss CNVs that are present in only one patient in the cohort but have additional evidence of pathogenicity, including extremely rare large and/or de novo CNVs. The candidate genes within these predicted disease-causing CNVs form functional networks with other known CDH genes and play putative roles in DNA binding/transcription regulation and embryonic development. These data substantiate the importance of CNVs in the etiology of CDH, identify CDH candidate genes and pathways, and highlight the importance of ongoing analysis of CNVs in the study of CDH and other structural birth defects.

Efficiency and problems of distance learning: Experience of Russia and Kazakhstan

2021 ◽  
pp. 21-32
Author(s):  
A. S. Adzhemov ◽  
A. B. Denisova ◽  
D. Zh. Satybaldina ◽  
Sh. Zh. Seilov
Keyword(s):  
Distance Learning ◽  
Large Scale ◽  
Learning Experience ◽  
Systematic Analysis ◽  
Limited Mobility ◽  
Existing Problems ◽  
Teachers And Students ◽  
National University ◽  
E Learning ◽  
Distance Work

The last decade has been marked by large-scale and rapid changes in education, taking place on the basis of modern infocommunication and digital technologies, new hardware and software, as well as teaching methods updated in accordance with this. The limited mobility of citizens due to the coronavirus pandemic further intensified these processes, when, even with a low readiness of educational institutions to switch to distance (electronic, remote) technologies, teachers and students had to quickly master these technologies and use them in practice. The resulting experience allows us to identify not only problematic, sometimes even negative, features of distance learning, but also to make sure of the undoubted advantages of these technologies. The article points out the need for a systematic analysis when deciding on the use of e-learning, taking into account both technical and methodological, as well as personnel readiness for the implementation of this technology.The article analyzes these problems using the example of teaching both technical and humanitarian disciplines. The experience of distance work is analyzed on the example of cooperation between the Moscow Technical University of Communications and Informatics (Russia) and the L. N. Gumilyov Eurasian National University (Kazakhstan), which in its practical activities purposefully invites foreign professors to deliver lectures, guide undergraduates, etc., including those based on distance technology. The data of an anonymous questionnaire survey of students of these universities are given, allowing to assess the effectiveness of the decisions made, as well as to clarify the existing problems.

Understanding the effectiveness of measures aiming to stabilize urban gullies in Congolese cities: a systematic analysis based on field surveys

2021 ◽  
Author(s):  
Eric Lutete Landu ◽  
Guy Ilombe Mawe ◽  
Charles Bielders ◽  
Fils Makanzu Imwangana ◽  
Olivier Dewitte ◽  
...  
Keyword(s):  
Large Scale ◽  
Clayey Soil ◽  
Waste Material ◽  
Control Measures ◽  
Household Waste ◽  
Small Scale ◽  
Systematic Analysis ◽  
Tropical Environments ◽  
Retention Ponds ◽  
Local Initiatives

<p>Many cities of the D.R. Congo are strongly affected by urban mega gullies. There are currently hundreds of such gullies in Kinshasa, Kikwit and Bukavu, representing a cumulative length of >200 km. Many of these gullies (typically tens of meters wide and deep) continue to expand, causing major damage to houses and other infrastructure and often claim human casualties. To mitigate these impacts, numerous measures are being implemented. The type and scale of these measures varies widely: from large structural measures like retention ponds to local initiatives of stabilizing gully heads with waste material. Nonetheless, earlier work indicates that an estimated 50% of the existing urban gullies continue to expand, despite the implementation of such measures. As such, we currently have very limited insight into the effectiveness of these measures and the overall best strategies to prevent and mitigate urban gullies. One reason for this is that most initiatives to stabilize urban gullies happen on a rather isolated basis and are rarely evaluated afterwards.</p><p>This work aims to improve our understanding of this issue. For this, we constructed a large inventory of measures implemented to stabilize urban gullies in Kinshasa, Kikwit and Bukavu and statistically confronted these measures with observed vegetation recovery and long-term gully expansion rates (derived from high-resolution imagery over a period of >14 years). Our preliminary results (based on a dataset of > 900 urban gullies) shows that the most commonly applied measures are revegetation and reinforcement of gully heads with sandbags or household waste material (implemented in around 65% of the cases). Retention ponds in streets and infiltration pits on house parcels are also frequently implemented (around 25% of the cases). Overall, techniques relying on vegetation are used relatively more frequently in regions with clayey soil, while techniques involving digging (e.g. infiltration pits) and topographic remodeling (e.g. gully reshaping by creation of terraces) are used mainly in sandy or sandy-clay areas. Surprisingly, small-scale local initiatives, such as stabilizing gully heads with household waste, often appear to have a higher effectivity than some large-scale civil engineering initiatives. However, such small-scale initiatives can come with important additional impacts (e.g. sanitation concerns). More research is needed to confirm these findings. Furthermore, the stability of gullies seems to be strongly linked to the degree of vegetation cover near the gully head. Nonetheless, it is not always clear if vegetation is the cause or the result of this stability. Overall, this study provides one of the first large scale assessments of the effectiveness of gully control measures in urban tropical environments. With this study, we hope to contribute to a better prevention and mitigation of this problem that affects many cities of the tropical Global South.</p>

Integrative Analysis of shared Genetic Pathogenesis by Autism Spectrum Disorder and Obsessive-Compulsive Disorder

2019 ◽  
Author(s):  
Dongbai Liu ◽  
Hongbao Cao ◽  
Kamil Can Kural ◽  
Qi Fang ◽  
Fuquan Zhang
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Large Scale ◽  
Genetic Network ◽  
Autism Spectrum ◽  
P Value ◽  
Genetic Associations ◽  
Obsessive Compulsive ◽  
Systematic Analysis ◽  
Gene Markers ◽  
Compulsive Disorder

Abstract Background Many common pathological features have been observed for both autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). However, no systematic analysis of the common gene markers associated both ASD and OCD has been conducted so far. Results Here, two batches of large-scale literature based disease-gene relation data (updated in 2017 and 2019, respectively) and gene expression data were integrated to study the possible association between OCD and ASD at the genetic level. Genes linked to OCD and ASD present significant overlap (p-value<2.64e-39). A genetic network of over 20 genes was constructed, through which OCD and ASD may exert influence on each other. The 2017-based analysis suggested six potential common risk genes for OCD and ASD (CDH2, ADCY8, APOE, TSPO, TOR1A, and OLIG2), and the 2019-based study identified two more genes (DISP1 and SETD1A). Notably, the gene APOE identified by the 2017-based analysis has been implicated to have an association with ASD in a recently study (2018) with DNA methylation analysis. Conclusions Our results support the possible complex genetic associations between OCD and ASD. Genes linked to one disease is worthy of further investigation as potential risk factors for the other.

Mining Protein Interactome Networks to Measure Interaction Reliability and Select Hub Proteins

2013 ◽  
pp. 222-238
Author(s):  
Young-Rae Cho ◽  
Aidong Zhang
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Functional Characterization ◽  
Flow Simulation ◽  
Protein Protein Interactions ◽  
Systematic Analysis ◽  
Graph Theoretic ◽  
Interactome Network ◽  
Protein Interactome ◽  
Hub Proteins

High-throughput techniques involve large-scale detection of protein-protein interactions. This interaction data set from the genome-scale perspective is structured into an interactome network. Since the interaction evidence represents functional linkage, various graph-theoretic computational approaches have been applied to the interactome networks for functional characterization. However, this data is generally unreliable, and the typical genome-wide interactome networks have a complex connectivity. In this paper, the authors explore systematic analysis of protein interactome networks, and propose a $k$-round signal flow simulation algorithm to measure interaction reliability from connection patterns of the interactome networks. This algorithm quantitatively characterizes functional links between proteins by simulating the propagation of information signals through complex connections. In this regard, the algorithm efficiently estimates the strength of alternative paths for each interaction. The authors also present an algorithm for mining the complex interactome network structure. The algorithm restructures the network by hierarchical ordering of nodes, and this structure re-formatting process reveals hub proteins in the interactome networks. This paper demonstrates that two rounds of simulation accurately scores interaction reliability in terms of ontological correlation and functional consistency. Finally, the authors validate that the selected structural hubs represent functional core proteins.

scholarly journals Faraday rotation measures of Northern hemisphere pulsars using CHIME/Pulsar

2020 ◽  
Vol 496 (3) ◽  
pp. 2836-2848 ◽  
Author(s):  
C Ng ◽  
A Pandhi ◽  
A Naidu ◽  
E Fonseca ◽  
V M Kaspi ◽  
...  
Keyword(s):  
Northern Hemisphere ◽  
Faraday Rotation ◽  
Large Scale ◽  
Galactic Plane ◽  
High Signal ◽  
First Year ◽  
Systematic Analysis ◽  
Intensity Mapping ◽  
Rotation Measure ◽  
High Cadence

ABSTRACT Using commissioning data from the first year of operation of the Canadian Hydrogen Intensity Mapping Experiment’s (CHIME) Pulsar backend system, we conduct a systematic analysis of the Faraday Rotation Measure (RM) of the Northern hemisphere pulsars detected by CHIME. We present 55 new RMs as well as obtain improved RM uncertainties for 25 further pulsars. CHIME’s low observing frequency and wide bandwidth between 400 and 800 MHz contribute to the precision of our measurements, whereas the high cadence observation provides extremely high signal-to-noise co-added data. Our results represent a significant increase of the pulsar RM census, particularly regarding the Northern hemisphere. These new RMs are for sources that are located in the Galactic plane out to 10 kpc, as well as off the plane to a scale height of ∼16 kpc. This improved knowledge of the Faraday sky will contribute to future Galactic large-scale magnetic structure and ionosphere modelling.

scholarly journals Contemporary large-scale international design competitions1 in China. A case study of Baietan, Guangzhou

2013 ◽  
Vol 6 (4) ◽  
Author(s):  
Zheng Liang ◽  
Raine Mäntysalo
Keyword(s):  
Large Scale ◽  
Integrated Approach ◽  
Public Access ◽  
Systematic Analysis ◽  
Planning And Design ◽  
Trading Zones ◽  
Culture Gap ◽  
Urban Planning And Design ◽  
Competition Rules ◽  
Political Background

The importance of contemporary design competitions has been increasingly recognized in fast-growing China in the course of World Trade Organization (WTO) integration and globalization. However, scientific and systematic analysis is rare on how international design competitions are introduced, and how they interact and transplant in the Chinese context. The well-known Chinese-Western culture gap and complicated social and political background make this topic more challenging. Herein, the authors focus on how the international design competitions were “translated” into both international and local perspectives with a compara­tive analysis on development of international design competitions between the Chinese and the Finnish model. To fully exemplify the design-completion procedure and the different roles of Chinese stakeholders and their perspectives on design competitions, the authors study the Baietan case, which was chosen due to its specific relationship with the city’s strategic plan, its representativeness in using international design competitions in connection to large-scale urban projects in China and its public access to the relevant documentation. The preliminary findings suggest that Chinese-style design competitions, acting as ‘designed trading zones’, with less-defined competition rules compared to the Finnish model, may foster the settings of local transformation in adopting international urban planning and design knowledge. However, an integrated approach is required to address subsequent implementation.

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