scholarly journals Bifurcations and mutation hot-spots in SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Xubiao Peng ◽  
Antti J. Niemi
Keyword(s):  
Hot Spots ◽  
Large Scale ◽  
Hot Spot ◽  
Data Bank ◽  
High Rate ◽  
Spike Protein ◽  
Novel Approach ◽  
Promising Target ◽  
Protein Research ◽  
Local Topology

AbstractThe spike protein is a most promising target for the development of vaccines and therapeutic drugs against the SARS-CoV-2 infection. But the apparently high rate of mutations makes the development of antiviral inhibitors a challenge. Here a methodology is presented to try and predict mutation hot-spot sites, where a small local change in spike protein’s structure can lead to a large scale conformational effect, and change the protein’s biological function. The methodology starts with a systematic physics based investigation of the spike protein’s Cα backbone in terms of its local topology. This topological investigation is then combined with a statistical examination of the pertinent backbone fragments; the statistical analysis builds on a comparison with high resolution Protein Data Bank (PDB) structures. Putative mutation hot-spot sites are identified as proximal sites to bifurcation points that can change the local topology of the Cα backbone in an essential manner. The likely outcome of a mutation, if it indeed occurs, is predicted by a comparison with residues in best-matching PDB fragments together with general stereochemical considerations. The detailed methodology is developed using the already observed D614G mutation as an example. This is a mutation that could have been correctly predicted by the present approach. Several additional examples of potential hot-spot residues are identified and analyzed in detail, some of them are found to be even better candidates for a mutation hot-spot than D614G.Significance statementA novel approach to predict mutation hot-spots in SARS-CoV-2 spike protein is presented. The approach introduces new topology based techniques to biophysical protein research. For a proof-of-concept the approach is described with the notorious D614G mutation of the spike protein as an example. It is shown that this mutation could have been correctly predicted by the present methods. Several additional mutation hot-spots are then identified and a number of them are shown to be topologically similar to the observed D614G mutation. The methodology can be used to design effective drugs and antibodies against the spike protein. It can also be employed more generally, whenever one needs to search for and identify mutation hot-spots in a protein.

scholarly journals Local topology and bifurcation hot-spots in proteins with SARS-CoV-2 spike protein as an example

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257886
Author(s):  
Xubiao Peng ◽  
Antti J. Niemi
Keyword(s):  
Hot Spots ◽  
Biological Function ◽  
Hot Spot ◽  
Data Bank ◽  
Spike Protein ◽  
Protein Backbone ◽  
Topological Methods ◽  
Expected Outcome ◽  
Protein Research ◽  
Local Topology

Novel topological methods are introduced to protein research. The aim is to identify hot-spot sites where a bifurcation can alter the local topology of the protein backbone. Since the shape of a protein is intimately related to its biological function, a substitution that causes a bifurcation should have an enhanced capacity to change the protein’s function. The methodology applies to any protein but it is developed with the SARS-CoV-2 spike protein as a timely example. First, topological criteria are introduced to identify and classify potential bifurcation hot-spot sites along the protein backbone. Then, the expected outcome of asubstitution, if it occurs, is estimated for a general class of hot-spots, using a comparative analysis of the surrounding backbone segments. The analysis combines the statistics of structurally commensurate amino acid fragments in the Protein Data Bank with general stereochemical considerations. It is observed that the notorious D614G substitution of the spike protein is a good example of a bifurcation hot-spot. A number of topologically similar examples are then analyzed in detail, some of them are even better candidates for a bifurcation hot-spot than D614G. The local topology of the more recently observed N501Y substitution is also inspected, and it is found that this site is proximal to a different kind of local topology changing bifurcation.

scholarly journals A novel approach to detect hot-spots in large-scale multivariate data

2007 ◽  
Vol 8 (1) ◽  
pp. 331 ◽  
Author(s):  
Jianhua Wu ◽  
Keith M Kendrick ◽  
Jianfeng Feng
Keyword(s):  
Hot Spots ◽  
Large Scale ◽  
Multivariate Data ◽  
Novel Approach

scholarly journals Computationally identifying hot spots in protein-DNA binding interfaces using an ensemble approach

2020 ◽  
Vol 21 (S13) ◽  
Author(s):  
Yuliang Pan ◽  
Shuigeng Zhou ◽  
Jihong Guan
Keyword(s):  
Dna Binding ◽  
Hot Spots ◽  
Large Scale ◽  
Binding Free Energy ◽  
Hot Spot ◽  
Dna Interaction ◽  
Computational Method ◽  
Dna Complexes ◽  
Binding Interface ◽  
Binding Interfaces

Abstract Background Protein-DNA interaction governs a large number of cellular processes, and it can be altered by a small fraction of interface residues, i.e., the so-called hot spots, which account for most of the interface binding free energy. Accurate prediction of hot spots is critical to understand the principle of protein-DNA interactions. There are already some computational methods that can accurately and efficiently predict a large number of hot residues. However, the insufficiency of experimentally validated hot-spot residues in protein-DNA complexes and the low diversity of the employed features limit the performance of existing methods. Results Here, we report a new computational method for effectively predicting hot spots in protein-DNA binding interfaces. This method, called PreHots (the abbreviation of Predicting Hotspots), adopts an ensemble stacking classifier that integrates different machine learning classifiers to generate a robust model with 19 features selected by a sequential backward feature selection algorithm. To this end, we constructed two new and reliable datasets (one benchmark for model training and one independent dataset for validation), which totally consist of 123 hot spots and 137 non-hot spots from 89 protein-DNA complexes. The data were manually collected from the literature and existing databases with a strict process of redundancy removal. Our method achieves a sensitivity of 0.813 and an AUC score of 0.868 in 10-fold cross-validation on the benchmark dataset, and a sensitivity of 0.818 and an AUC score of 0.820 on the independent test dataset. The results show that our approach outperforms the existing ones. Conclusions PreHots, which is based on stack ensemble of boosting algorithms, can reliably predict hot spots at the protein-DNA binding interface on a large scale. Compared with the existing methods, PreHots can achieve better prediction performance. Both the webserver of PreHots and the datasets are freely available at: http://dmb.tongji.edu.cn/tools/PreHots/.

The Long-Term and System-Level Impacts of Institutionalizing Hot Spot Policing in a Small City

2021 ◽  
Author(s):  
Christopher S Koper ◽  
Cynthia Lum ◽  
Xiaoyun Wu ◽  
Tim Hegarty
Keyword(s):  
Hot Spots ◽  
Large Scale ◽  
Hot Spot ◽  
System Level ◽  
Small City ◽  
Police Agency ◽  
Large Cities ◽  
Quasi Experimental

Abstract Numerous studies have shown that hot spot policing (HSP) is effective in reducing crime in small high-risk locations. However, questions remain about the efficacy of HSP outside large cities, its long-term sustainability and effects, and its ability to produce aggregate reductions in crime across large areas. This study highlights a small city police agency that has sustained a systematic, citywide HSP patrol strategy since 2013. A quasi-experimental assessment using nearly 7 years of follow-up data shows the programme reduced crime in targeted hot spots without displacement. Citywide, citizen calls about crime and disorder fell by 14%, with reductions ranging from 12% for disorder calls to 41% for violence calls. This study shows the value of HSP in smaller jurisdictions and supports the theory that HSP can produce large-scale, long-term reductions in crime and disorder when practiced in a manner that has sufficient targeting, dosage, tracking, management, and commitment from leadership.

scholarly journals Clustering of Mycobacterium avium subsp. paratuberculosis in Rabbits and the Environment: How Hot Is a Hot Spot?

2005 ◽  
Vol 71 (10) ◽  
pp. 6033-6038 ◽  
Author(s):  
Johanna Judge ◽  
Ilias Kyriazakis ◽  
Alastair Greig ◽  
David J. Allcroft ◽  
Michael R. Hutchings
Keyword(s):  
Mycobacterium Avium ◽  
Hot Spots ◽  
Large Scale ◽  
Temporal Dynamics ◽  
Hot Spot ◽  
Temporal Distribution ◽  
Interspecies Transmission ◽  
Environmental Distribution ◽  
Cyclical Pattern ◽  
Mycobacterium Avium Subsp Paratuberculosis

ABSTRACT Clustering of pathogens in the environment leads to hot spots of diseases at local, regional, national, and international levels. Scotland contains regional hot spots of Johne's disease (caused by Mycobacterium avium subsp. paratuberculosis) in rabbits, and there is increasing evidence of a link between paratuberculosis infections in rabbits and cattle. The spatial and temporal dynamics of paratuberculosis in rabbits within a hot spot region were studied with the overall aim of determining environmental patterns of infection and thus the risk of interspecies transmission to livestock. The specific aims were to determine if prevalence of paratuberculosis in rabbits varies temporally between seasons and whether the heterogeneous spatial environmental distribution of M. avium subsp. paratuberculosis on a large scale (i.e., regional hot spots) is replicated at finer resolutions within a hot spot. The overall prevalence of M. avium subsp. paratuberculosis in rabbits was 39.7%; the temporal distribution of infection in rabbits followed a cyclical pattern, with a peak in spring of 55.4% and a low in summer of 19.4%. Spatially, M. avium subsp. paratuberculosis-infected rabbits and, thus, the risk of interspecies transmission were highly clustered in the environment. However, this is mostly due to the clustered distribution of rabbits. The patterns of M. avium subsp. paratuberculosis infection in rabbits are discussed in relation to the host's socioecology and risk to livestock.

scholarly journals Potential Application of Hough Transform to Extract Hot Spot Delineated Boundaries using Landsat-8 Satellite Images

2020 ◽  
Vol 9 (3) ◽  
pp. 3550-3557
Keyword(s):  
Hough Transform ◽  
Hot Spots ◽  
Large Scale ◽  
Hot Spot ◽  
Satellite Image ◽  
Detection Algorithm ◽  
Landsat 8 ◽  
Spot Detection ◽  
Canny Edge ◽  
Satellite Image Analysis

Coal fires, also known as subsurface fires or hot spots are all-inclusive issues in coal mines everywhere throughout the globe. Aimless mining over a period of past 100 years has prompted large scale damages to the ecosystem of the earth. For example, debasement in nature of water, soil, air, vegetation dissemination and variations in land topography have caused degradation. Research is needed to be more attentive on developing the prospective use of the satellite image analysis for hot spot detection because ground-based hot spots monitoring is time-taking, complex, cumbrous and very expensive. In this paper, a two-stage model has been developed to extract the hot spot delineated boundaries in Jharia coal field (JCF) region. In the first stage, contextual thresholding (CT) technique has been used to classify the hot spot and non-hot spot regions. After thorough processing, hot spots regions have been retrieved and for performance evaluation sensitivity and specificity are calculated, which suggest that hot spots were detected accurately in successful and efficient way. In second stage, the Canny edge detection algorithm is applied to detect the edges of the hot spot regions and then the binary image is generated, which is later converted into a vector image. Finally Hough transform is implemented on the obtained vector images for delineating hot spot boundaries. In future, delineated hot spot boundaries may be used to obtain the expansion or shrinking information of hot spot regions and it can be used for area estimation also.

scholarly journals Identifying Large Scale Features on the Surface of Contact Binaries with Sub-Arcsecond Techniques

2001 ◽  
Vol 205 ◽  
pp. 314-315
Author(s):  
P.G. Niarchos ◽  
I. Pustylnik
Keyword(s):  
Large Scale ◽  
Hot Spot ◽  
X Rays ◽  
Surface Features ◽  
Trigonometric Parallax ◽  
Preferential Site ◽  
Promising Target ◽  
Optical Region ◽  
Contact Binaries ◽  
Contact Binary

We summarize multifold evidence for the presence of a hot spot region in contact binary VW Cephei. We interpret this feature as a photospheric burn and the preferential site of flares in EUV and X rays. With its trigonometric parallax of 0.041 arcsec VW Cep is a promising target for a milliarcsecond resolution investigation of the nature of surface features both in optical region and in IR.

scholarly journals Human Immunodeficiency Virus Type 1 Recombination: Rate, Fidelity, and Putative Hot Spots

2002 ◽  
Vol 76 (22) ◽  
pp. 11273-11282 ◽  
Author(s):  
Jianling Zhuang ◽  
Amanda E. Jetzt ◽  
Guoli Sun ◽  
Hong Yu ◽  
George Klarmann ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Sequencing ◽  
Human Immunodeficiency Virus Type ◽  
Hot Spots ◽  
Hot Spot ◽  
High Rate ◽  
Vector System ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Previously, we reported that human immunodeficiency virus type 1 (HIV-1) recombines approximately two to three times per genome per replication cycle, an extremely high rate of recombination given the relatively small genome size of HIV-1. However, a recombination hot spot involving sequence of nonretroviral origin was identified in the vector system utilized, raising the possibility that this hot spot skewed the rate of recombination, and the rate of recombination observed was an overestimation. To address this issue, an HIV-1-derived vector system was used to examine the rate of recombination between autologous HIV-1 sequences after restricting replication to a single cycle in the absence of this hot spot. Viral DNA and RNA were analyzed by a combination of the heteroduplex tracking assay, restriction enzyme analysis, DNA sequencing, and reverse transcription-PCR. The results indicate that HIV-1 undergoes recombination at a minimum rate of 2.8 crossovers per genome per cycle. Again, this is a very high rate given the small size of the HIV-1 genome. The results also suggested that there might be local hot spots of recombination at different locations throughout the genome since 13 of the 33 strand transfers identified by DNA sequencing shared the same site of recombination with one or two other clones. Furthermore, identification of crossover segments also allowed examination of mutations at the point of recombination, since it has been predicted from some studies of cell-free systems that mutations may occur with a frequency of 30 to 50% at crossover junctions. However, DNA sequence analysis of crossover junctions indicated that homologous recombination during viral replication was not particularly mutagenic, indicating that there are other factors or conditions not yet reproduced in cell-free systems which contribute to fidelity during retroviral recombination.

Community-Wide Prevention of COVID-19: A Systematic Analysis of Hot vs. Cold Spots

2021 ◽  
Author(s):  
Mackenzie Davis ◽  
E Scott Geller ◽  
Zach Mastrich
Keyword(s):  
Hot Spots ◽  
Large Scale ◽  
Hot Spot ◽  
Virginia Tech ◽  
University Of Kansas ◽  
Prevention Measures ◽  
Systematic Analysis ◽  
University Of Florida ◽  
Western Michigan University ◽  
Cold Spots

Universities in five different states are collaborating on an original large-scale COVID-prevention effort by asking many of their students to complete an innovative survey that strategically asks them to identify areas on and around campus that are “hot spots” for spreading the coronavirus. These universities—Virginia Tech, Appalachian State, Western Michigan, University of Kansas, and University of Florida—are also observing mask wearing, social distancing, and other COVID prevention measures in their communities to analyze the risk management and wellness precautions taken by students, faculty, and the surrounding communities. Mapping hot-spot areas provides invaluable information for prevention and intervention creation.

scholarly journals How Do Ocean Warm Anomalies Favor the Aggregation of Deep Convective Clouds?

2020 ◽  
Vol 77 (11) ◽  
pp. 3733-3745
Author(s):  
Sara Shamekh ◽  
Caroline Muller ◽  
Jean-Philippe Duvel ◽  
Fabio D’Andrea
Keyword(s):  
Hot Spots ◽  
Large Scale ◽  
Hot Spot ◽  
Spot Size ◽  
Large Scale Circulation ◽  
Convective Clouds ◽  
Sst Anomaly ◽  
Radiative Feedbacks ◽  
Self Aggregation

AbstractWe investigate the role of a warm sea surface temperature (SST) anomaly (hot spot of typically 3 to 5 K) on the aggregation of convection using cloud-resolving simulations in a nonrotating framework. It is well known that SST gradients can spatially organize convection. Even with uniform SST, the spontaneous self-aggregation of convection is possible above a critical SST (here 295 K), arising mainly from radiative feedbacks. We investigate how a circular hot spot helps organize convection, and how self-aggregation feedbacks modulate this organization. The hot spot significantly accelerates aggregation, particularly for warmer/larger hot spots, and extends the range of SSTs for which aggregation occurs; however, at cold SST (290 K) the aggregated cluster disaggregates if we remove the hot spot. A large convective instability over the hot spot leads to stronger convection and generates a large-scale circulation which forces the subsidence drying outside the hot spot. Indeed, convection over the hot spot brings the atmosphere toward a warmer temperature. The warmer temperatures are imprinted over the whole domain by gravity waves and subsidence warming. The initial transient warming and concomitant subsidence drying suppress convection outside the hot spot, thus driving the aggregation. The hot-spot-induced large-scale circulation can enforce the aggregation even without radiative feedbacks for hot spots sufficiently large/warm. The strength of the large-scale circulation, which defines the speed of aggregation, is a function of the hot spot fractional area. At equilibrium, once the aggregation is well established, the moist convective region with upward midtropospheric motion, centered over the hot spot, has an area surprisingly independent of the hot spot size.

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