scholarly journals SANTA-SIM: Simulating Viral Sequence Evolution Dynamics Under Selection and Recombination

2018 ◽  
Author(s):  
Abbas Jariani ◽  
Christopher Warth ◽  
Koen Deforche ◽  
Pieter Libin ◽  
Alexei J Drummond ◽  
...  
Keyword(s):  
Software Package ◽  
Point Mutations ◽  
Sequence Evolution ◽  
Biological Processes ◽  
Viral Sequence ◽  
Recombination Point ◽  
Wide Range ◽  
Cross Platform ◽  
Evolution Dynamics ◽  
Inference Methods

AbstractSimulations are widely used to provide expectations and predictive distributions under known conditions against which to compare empirical data. Such simulations are also invaluable for testing and comparing the behavior and power of inference methods. We describe SANTA-SIM, a software package to simulate the evolution of a population of gene sequences forwards through time. It models the underlying biological processes as discrete components: replication, recombination, point mutations, insertion-deletions, and selection under various fitness models and population size dynamics. The software is designed to be intuitive to work with for a wide range of users and executable in a cross-platform manner.

scholarly journals SANTA-SIM: simulating viral sequence evolution dynamics under selection and recombination

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Abbas Jariani ◽  
Christopher Warth ◽  
Koen Deforche ◽  
Pieter Libin ◽  
Alexei J Drummond ◽  
...  
Keyword(s):  
Software Package ◽  
Point Mutations ◽  
Sequence Evolution ◽  
Biological Processes ◽  
Viral Sequence ◽  
Recombination Point ◽  
Wide Range ◽  
Cross Platform ◽  
Evolution Dynamics ◽  
Inference Methods

Abstract Simulations are widely used to provide expectations and predictive distributions under known conditions against which to compare empirical data. Such simulations are also invaluable for testing and comparing the behaviour and power of inference methods. We describe SANTA-SIM, a software package to simulate the evolution of a population of gene sequences forwards through time. It models the underlying biological processes as discrete components: replication, recombination, point mutations, insertion–deletions, and selection under various fitness models and population size dynamics. The software is designed to be intuitive to work with for a wide range of users and executable in a cross-platform manner.

scholarly journals psupertime: supervised pseudotime inference for single cell RNA-seq data with sequential labels

2019 ◽  
Author(s):  
Will Macnair ◽  
Manfred Claassen
Keyword(s):  
Single Cell ◽  
Biological Processes ◽  
Rna Seq ◽  
Batch Effects ◽  
Substantial Variation ◽  
Wide Range ◽  
Time Series Studies ◽  
Development And Differentiation ◽  
Inference Methods ◽  
Simple Regression

AbstractSingle cell RNA-seq has been successfully combined with pseudotime inference methods to investigate biological processes which have sequential labels, such as time series studies of development and differentiation. Pseudotime methods developed to date ignore the labels, and where there is substantial variation in the data not associated with the labels (such as cell cycle variation or batch effects), they can fail to find relevant genes. We introduce psupertime, a supervised pseudotime approach which outperforms benchmark pseudotime methods by explicitly using the sequential labels as input. psupertime uses a simple, regression-based model, which by acknowledging the labels assures that genes relevant to the process, rather than to major drivers of variation, are found. psupertime is applicable to the wide range of single cell RNA-seq datasets with sequential labels, derived from either experimental design or user-selected cell cluster sequences, and provides a tool for targeted identification of genes regulated along biological processes.

scholarly journals Identifying Conserved Generic Aspergillus spp. Co-Expressed Gene Modules Associated with Germination Using Cross-Platform and Cross-Species Transcriptomics

2021 ◽  
Vol 7 (4) ◽  
pp. 270
Author(s):  
Tim J. H. Baltussen ◽  
Jordy P. M. Coolen ◽  
Paul E. Verweij ◽  
Jan Dijksterhuis ◽  
Willem J. G. Melchers
Keyword(s):  
Comparative Analysis ◽  
Expression Patterns ◽  
Biological Processes ◽  
Polarized Growth ◽  
Black Module ◽  
Cross Platform ◽  
Gene Modules ◽  
Opportunistic Human Pathogen ◽  
Dependent Transport ◽  
Blue Module

Aspergillus spp. is an opportunistic human pathogen that may cause a spectrum of pulmonary diseases. In order to establish infection, inhaled conidia must germinate, whereby they break dormancy, start to swell, and initiate a highly polarized growth process. To identify critical biological processes during germination, we performed a cross-platform, cross-species comparative analysis of germinating A. fumigatus and A. niger conidia using transcriptional data from published RNA-Seq and Affymetrix studies. A consensus co-expression network analysis identified four gene modules associated with stages of germination. These modules showed numerous shared biological processes between A. niger and A. fumigatus during conidial germination. Specifically, the turquoise module was enriched with secondary metabolism, the black module was highly enriched with protein synthesis, the darkgreen module was enriched with protein fate, and the blue module was highly enriched with polarized growth. More specifically, enriched functional categories identified in the blue module were vesicle formation, vesicular transport, tubulin dependent transport, actin-dependent transport, exocytosis, and endocytosis. Genes important for these biological processes showed similar expression patterns in A. fumigatus and A. niger, therefore, they could be potential antifungal targets. Through cross-platform, cross-species comparative analysis, we were able to identify biologically meaningful modules shared by A. fumigatus and A. niger, which underscores the potential of this approach.

scholarly journals Energetics of mesoscale cell turbulence in two-dimensional monolayers

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shao-Zhen Lin ◽  
Wu-Yang Zhang ◽  
Dapeng Bi ◽  
Bo Li ◽  
Xi-Qiao Feng
Keyword(s):  
Kinetic Energy ◽  
Tumor Metastasis ◽  
Cell Types ◽  
Boltzmann Distribution ◽  
Scaling Exponent ◽  
Biological Processes ◽  
Two Dimensional ◽  
Cell Monolayers ◽  
Wide Range ◽  
Epithelial Cell Monolayers

AbstractInvestigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

scholarly journals Privacy-Aware Multidimensional Mobile Service Quality Prediction and Recommendation in Distributed Fog Environment

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Wenwen Gong ◽  
Lianyong Qi ◽  
Yanwei Xu
Keyword(s):  
Service Selection ◽  
Locality Sensitive Hashing ◽  
Mobile Service ◽  
Service Recommendation ◽  
User Privacy ◽  
Service Usage ◽  
Selection Decisions ◽  
Wide Range ◽  
Cross Platform ◽  
Computational Resources

With the ever-increasing popularity of mobile computing technology, a wide range of computational resources or services (e.g., movies, food, and places of interest) are migrating to the mobile infrastructure or devices (e.g., mobile phones, PDA, and smart watches), imposing heavy burdens on the service selection decisions of users. In this situation, service recommendation has become one of the promising ways to alleviate such burdens. In general, the service usage data used to make service recommendation are produced by various mobile devices and collected by distributed edge platforms, which leads to potential leakage of user privacy during the subsequent cross-platform data collaboration and service recommendation process. Locality-Sensitive Hashing (LSH) technique has recently been introduced to realize the privacy-preserving distributed service recommendation. However, existing LSH-based recommendation approaches often consider only one quality dimension of services, without considering the multidimensional recommendation scenarios that are more complex but more common. In view of this drawback, we improve the traditional LSH and put forward a novel LSH-based service recommendation approach named SerRecmulti-qos, to protect users’ privacy over multiple quality dimensions during the distributed mobile service recommendation process.

scholarly journals Reversing resistance: different routes and common themes across pathogens

2017 ◽  
Vol 284 (1863) ◽  
pp. 20171619 ◽  
Author(s):  
Richard C. Allen ◽  
Jan Engelstädter ◽  
Sebastian Bonhoeffer ◽  
Bruce A. McDonald ◽  
Alex R. Hall
Keyword(s):  
Fitness Cost ◽  
Biological Processes ◽  
Short Supply ◽  
Compensatory Evolution ◽  
Wide Range ◽  
Different Types ◽  
Cost Of Resistance

Resistance spreads rapidly in pathogen or pest populations exposed to biocides, such as fungicides and antibiotics, and in many cases new biocides are in short supply. How can resistance be reversed in order to prolong the effectiveness of available treatments? Some key parameters affecting reversion of resistance are well known, such as the fitness cost of resistance. However, the population biological processes that actually cause resistance to persist or decline remain poorly characterized, and consequently our ability to manage reversion of resistance is limited. Where do susceptible genotypes that replace resistant lineages come from? What is the epidemiological scale of reversion? What information do we need to predict the mechanisms or likelihood of reversion? Here, we define some of the population biological processes that can drive reversion, using examples from a wide range of taxa and biocides. These processes differ primarily in the origin of revertant genotypes, but also in their sensitivity to factors such as coselection and compensatory evolution that can alter the rate of reversion, and the likelihood that resistance will re-emerge upon re-exposure to biocides. We therefore argue that discriminating among different types of reversion allows for better prediction of where resistance is most likely to persist.

scholarly journals phastSim: efficient simulation of sequence evolution for pandemic-scale datasets

2021 ◽  
Author(s):  
Nicola De Maio ◽  
Lukas Weilguny ◽  
Conor R. Walker ◽  
Yatish Turakhia ◽  
Russell Corbett-Detig ◽  
...  
Keyword(s):  
Sequence Data ◽  
Search Tree ◽  
Sequence Evolution ◽  
Genomic Epidemiology ◽  
Efficient Simulation ◽  
Processing Power ◽  
Large Trees ◽  
Easy Integration ◽  
Inference Methods ◽  
High Computational Efficiency

AbstractSequence simulators are fundamental tools in bioinformatics, as they allow us to test data processing and inference tools, as well as being part of some inference methods. The ongoing surge in available sequence data is however testing the limits of our bioinformatics software. One example is the large number of SARS-CoV-2 genomes available, which are beyond the processing power of many methods, and simulating such large datasets is also proving difficult. Here we present a new algorithm and software for efficiently simulating sequence evolution along extremely large trees (e.g. > 100, 000 tips) when the branches of the tree are short, as is typical in genomic epidemiology. Our algorithm is based on the Gillespie approach, and implements an efficient multi-layered search tree structure that provides high computational efficiency by taking advantage of the fact that only a small proportion of the genome is likely to mutate at each branch of the considered phylogeny. Our open source software is available fromhttps://github.com/NicolaDM/phastSimand allows easy integration with other Python packages as well as a variety of evolutionary models, including new ones that we developed to more realistically model SARS-CoV-2 genome evolution.

scholarly journals The RhoA-ROCK pathway in the regulation of T and B cell responses

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2295 ◽  
Author(s):  
Edd Ricker ◽  
Luvana Chowdhury ◽  
Woelsung Yi ◽  
Alessandra B. Pernis
Keyword(s):  
Immune Responses ◽  
Biological Processes ◽  
Dynamic Interactions ◽  
Cell Responses ◽  
Important Mediator ◽  
Downstream Effectors ◽  
Wide Range ◽  
Response To Stress ◽  
The Impact ◽  
Rho Kinases

Effective immune responses require the precise regulation of dynamic interactions between hematopoietic and non-hematopoietic cells. The Rho subfamily of GTPases, which includes RhoA, is rapidly activated downstream of a diverse array of biochemical and biomechanical signals, and is emerging as an important mediator of this cross-talk. Key downstream effectors of RhoA are the Rho kinases, or ROCKs. The ROCKs are two serine-threonine kinases that can act as global coordinators of a tissue’s response to stress and injury because of their ability to regulate a wide range of biological processes. Although the RhoA-ROCK pathway has been extensively investigated in the non-hematopoietic compartment, its role in the immune system is just now becoming appreciated. In this commentary, we provide a brief overview of recent findings that highlight the contribution of this pathway to lymphocyte development and activation, and the impact that dysregulation in the activation of RhoA and/or the ROCKs may exert on a growing list of autoimmune and lymphoproliferative disorders.

scholarly journals Heteroplasmic Point Mutations of Mitochondrial DNA Affecting Subunit I of Cytochrome c Oxidase in Two Patients With Acquired Idiopathic Sideroblastic Anemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4961-4972 ◽  
Author(s):  
Norbert Gattermann ◽  
Stefan Retzlaff ◽  
Yan-Ling Wang ◽  
Götz Hofhaus ◽  
Jürgen Heinisch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Ferric Iron ◽  
Point Mutations ◽  
Polymorphism Analysis ◽  
Sideroblastic Anemia ◽  
Wide Range

Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA (mtDNA), because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron (Fe3+) to ferrous iron (Fe2+). The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. It is not yet understood to which part of the respiratory chain the reduction of ferric iron is linked. In two patients with AISA we identified point mutations of mtDNA affecting the same transmembrane helix within subunit I of cytochrome c oxidase (COX I; ie, complex IV of the respiratory chain). The mutations were detected by restriction fragment length polymorphism analysis and temperature gradient gel electrophoresis. One of the mutations involves a T → C transition in nucleotide position 6742, causing an amino acid change from methionine to threonine. The other mutation is a T → C transition at nt 6721, changing isoleucine to threonine. Both amino acids are highly conserved in a wide range of species. Both mutations are heteroplasmic, ie, they establish a mixture of normal and mutated mitochondrial genomes, which is typical of disorders of mtDNA. The mutations were present in bone marrow and whole blood samples, in isolated platelets, and in granulocytes, but appeared to be absent from T and B lymphocytes purified by immunomagnetic bead separation. They were not detected in buccal mucosa cells obtained by mouthwashes and in cultured skin fibroblasts examined in one of the patients. In both patients, this pattern of involvement suggests that the mtDNA mutation occurred in a self-renewing bone marrow stem cell with myeloid determination. Identification of two point mutations with very similar location suggests that cytochrome c oxidase plays an important role in the pathogenesis of AISA. COX may be the physiologic site of iron reduction and transport through the inner mitochondrial membrane.

scholarly journals Extending the Coding Potential of Viral Genomes with Overlapping Antisense ORFs: A Case for the De Novo Creation of the Gene Encoding the Antisense Protein ASP of HIV-1

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 146
Author(s):  
Angelo Pavesi ◽  
Fabio Romerio
Keyword(s):  
De Novo ◽  
Point Mutations ◽  
Selective Advantage ◽  
Genomic Region ◽  
Fine Tuning ◽  
Sequence Evolution ◽  
Viral Genomes ◽  
Stop Codons ◽  
Hiv 1

Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in response to strong selective pressure. The most frequent scenario involves two different reading frames in the same DNA strand (sense overlap). Much less frequent are cases of overlapping genes that are encoded on opposite DNA strands (antisense overlap). One such example is the antisense ORF, asp in the minus strand of the HIV-1 genome overlapping the env gene. The asp gene is highly conserved in pandemic HIV-1 strains of group M, and it is absent in non-pandemic HIV-1 groups, HIV-2, and lentiviruses infecting non-human primates, suggesting that the ~190-amino acid protein that is expressed from this gene (ASP) may play a role in virus spread. While the function of ASP in the virus life cycle remains to be elucidated, mounting evidence from several research groups indicates that ASP is expressed in vivo. There are two alternative hypotheses that could be envisioned to explain the origin of the asp ORF. On one hand, asp may have originally been present in the ancestor of contemporary lentiviruses, and subsequently lost in all descendants except for most HIV-1 strains of group M due to selective advantage. Alternatively, the asp ORF may have originated very recently with the emergence of group M HIV-1 strains from SIVcpz. Here, we used a combination of computational and statistical approaches to study the genomic region of env in primate lentiviruses to shed light on the origin, structure, and sequence evolution of the asp ORF. The results emerging from our studies support the hypothesis of a recent de novo addition of the antisense ORF to the HIV-1 genome through a process that entailed progressive removal of existing internal stop codons from SIV strains to HIV-1 strains of group M, and fine tuning of the codon sequence in env that reduced the chances of new stop codons occurring in asp. Altogether, the study supports the notion that the HIV-1 asp gene encodes an accessory protein, providing a selective advantage to the virus.

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