THREE-DIMENSIONAL DEFINITION OF LEAF MORPHOLOGICAL TRAITS OF ARABIDOPSIS IN SILICO PHENOTYPIC ANALYSIS

2005 ◽  
Vol 03 (02) ◽  
pp. 401-414 ◽  
Author(s):  
ELI KAMINUMA ◽  
NAOHIKO HEIDA ◽  
YUKO TSUMOTO ◽  
MIKI NAKAZAWA ◽  
NOBUHARU GOTO ◽  
...  
Keyword(s):  
In Silico ◽  
Morphological Traits ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Phenotypic Analysis ◽  
3 Dimensional ◽  
Functional Studies ◽  
Phenotypic Alteration ◽  
Definition Of ◽  
Leaf Morphological Traits

The detection of phenotypic alterations of mutants and variants is one of the bottlenecks that hinder systematic gene functional studies of the model plant Arabidopsis. In an earlier study, we have addressed this problem by proposing a novel methodology for phenome analysis based on in silico analysis of polygon models that are acquired by 3-dimensional (3D) measurement and which precisely reconstruct the actual plant shape. However, 3D quantitative descriptions of morphological traits are rare, whereas conventional 2D descriptions have already been studied but may lack the necessary precision. In this report, we focus on six major leaf morphological traits, which are commonly used in the current manual mutant screens, and propose new 3D quantitative definitions that describe these traits. In experiments to extract the traits, we found significant differences between two variants of Arabidopsis with respect to blade roundness and blade epinasty. Remarkably, the detected difference between variants in the blade roundness trait was undetectable when using conventional 2D descriptions. Thus, the result of the experiment indicates that the proposed definitions with 3D description may lead to new discoveries of phenotypic alteration in gene functional studies that would not be possible using conventional 2D descriptions.

scholarly journals Unmasking of novel mutations within XK gene that could be used as Diagnostic Markers to Predict McLeod syndrome: Using in silico analysis

2019 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Mohamed A. Hassan
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Structural Effect ◽  
Novel Mutations ◽  
Multisystem Disorder ◽  
Functional Studies ◽  
Central Nervous Systems ◽  
The One ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundMcLeod neuroacanthocytosis syndrome is a rare X-linked recessive multisystem disorder affecting the peripheral and central nervous systems, red blood cells, and internal organs.MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structural and functional level.Result2 novel mutations out of 104 nsSNPs that are found to be deleterious effect on the XK structure and function.ConclusionThe present study provided a novel insight into the understanding of McLeod syndrome, SNPs occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here; we prioritize SNPs for further genetic mapping studies. This will be a valuable resource for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.

Abstract 555: Functional Characterization Uncovered Novel Loss-of-function Mutations in ABCA1

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Xin Bi ◽  
James McParland ◽  
Jian Wang ◽  
Adam D McIntyre ◽  
Robert A Hegele ◽  
...  
Keyword(s):  
In Silico ◽  
Cholesterol Efflux ◽  
Functional Characterization ◽  
In Silico Analysis ◽  
Site Directed Mutagenesis ◽  
Loss Of Function ◽  
Wild Type ◽  
Functional Studies ◽  
Lipid Efflux

Objectives: ABCA1 encodes the membrane protein ATP-binding cassette transporter A1 (ABCA1), a pivotal player in nascent HDL formation via its ability to facilitate cholesterol and phospholipid efflux to apolipoprotein A-I (ApoA-I). ABCA1 variants are frequently found in subjects with primary hypoalphalipoproteinemia, however, their pathogenicity and causal link with the clinical phenotype are not always known. Methods: In silico analysis (Mutation Assessor, PANTHER, PolyPhen-2, PROVEAN, SIFT, and VEST) were performed to predict the functional consequences of ABCA1 missense variants found in our cohort of hypoalphalipoproteinemia. A subset of novel ABCA1 variants were generated in vitro through site-directed mutagenesis and their abilities in mediating lipid efflux to apoA-I were determined using standard methods. Results: A total of 32 mutations in ABCA1 were identified, among which 15 were classified as missense, 9 as nonsense or frameshift, 7 as intronic, and 1 as ”no-protein”. We selected 5 variants that were labeled as pathogenic or possibly pathogenic by in silico analysis to conduct functional studies. Two newly identified mutations in ABCA1, a nonsense mutation (p.E1005X) and a missense mutation (p.S2046R), resulted in complete loss of the canonical lipid efflux function of ABCA1 (2.5% and 1.8% of wild type cholesterol efflux level respectively). These results were concordant with the phenotypic characteristics of the carriers. Three additional mutations (p.G750W and p.R1341T and p.I1085F) resulted in only a partial loss of function (66-75% of wild type cholesterol efflux level). These results were somewhat discordant with the phenotype of the heterozygote carriers (HDL-C levels of 16, 14 and 38 mg/dl respectively), suggesting the presence of additional causal factors. Conclusions: These results support E1005X and S2046R as ABCA1 loss-of-function mutations and highlight the need to conduct functional studies on unknown variants to determine their pathogenicity.

In silico analysis of Nattokinase from Bacillus subtilis sp natto

2017 ◽  
Vol 9 (04) ◽  
Author(s):  
Cambyz Irajie ◽  
Milad Mohkam ◽  
Navid Nezafat ◽  
Fatemeh Mohammadi ◽  
Younes Ghasemi
Keyword(s):  
Bacillus Subtilis ◽  
Serine Protease ◽  
In Silico ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Dimensional Structure ◽  
Cardiovascular Therapy ◽  
And Function ◽  
Outlier Region ◽  
Silico Analysis

Nattokinase or subtilisin NAT (EC 3.4.21.62) is one of the most remarkable enzymes produced by Bacillus subtilis sp. Natto, which posses direct fibrinolytic activity. The aim of this study is in silico analysis of Nattokinase structure and function. The three-dimensional structure of serine protease Nattokinase from Bacillus subtilis sp. natto was determined using homology modeling performed by Geno3D2 Web Server and refined by ModRefiner. The obtained models were validated via programs such as RAMPAGE, ERRAT, 3D Match and verify 3D for consistency; moreover, functional analysis performed by PFP from Kihara Bioinformatics laboratory. RAMPAGE analysis showed that 96.7% of the residues are located in the favored region, 3.0% in allowed region and 0.4% in outlier region of the Ramachandran plot. The verify 3D value of 0.73 indicates that the environmental sketch of the model is fine. SOPMA and PSIPRED were exploited for computation of the secondary structural properties of serine protease Nattokinase. Active site determination via AADS suggested that this enzyme can be applied as a potent enzyme for cardiovascular therapy. However, these results should be more confirmed by wet lab researches for designing the more active enzyme for better functions on its fibrinolysis activity.

scholarly journals Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

2021 ◽  
Author(s):  
Maria Iqbal ◽  
Reza Maroofian ◽  
Büşranur Çavdarlı ◽  
Florence Riccardi ◽  
Michael Field ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Recessive ◽  
Neurodevelopmental Disorder ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Missense Variant ◽  
The Third ◽  
Dimerization Interface ◽  
Silico Analysis

Abstract Purpose We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. Methods We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. Results In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. Conclusion We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.

scholarly journals In Silico Analysis of Missense Mutations as a First Step in Functional Studies: Examples from Two Sphingolipidoses

2018 ◽  
Vol 19 (11) ◽  
pp. 3409 ◽  
Author(s):  
Ana Duarte ◽  
Diogo Ribeiro ◽  
Luciana Moreira ◽  
Olga Amaral
Keyword(s):  
Amino Acid ◽  
Protein Level ◽  
In Silico ◽  
In Silico Analysis ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Functional Studies ◽  
Analysis System ◽  
Silico Analysis

In order to delineate a better approach to functional studies, we have selected 23 missense mutations distributed in different domains of two lysosomal enzymes, to be studied by in silico analysis. In silico analysis of mutations relies on computational modeling to predict their effects. Various computational platforms are currently available to check the probable causality of mutations encountered in patients at the protein and at the RNA levels. In this work we used four different platforms freely available online (Protein Variation Effect Analyzer- PROVEAN, PolyPhen-2, Swiss-model Expert Protein Analysis System—ExPASy, and SNAP2) to check amino acid substitutions and their effect at the protein level. The existence of functional studies, regarding the amino acid substitutions, led to the selection of the distinct protein mutants. Functional data were used to compare the results obtained with different bioinformatics tools. With the advent of next-generation sequencing, it is not feasible to carry out functional tests in all the variants detected. In silico analysis seems to be useful for the delineation of which mutants are worth studying through functional studies. Therefore, prediction of the mutation impact at the protein level, applying computational analysis, confers the means to rapidly provide a prognosis value to genotyping results, making it potentially valuable for patient care as well as research purposes. The present work points to the need to carry out functional studies in mutations that might look neutral. Moreover, it should be noted that single nucleotide polymorphisms (SNPs), occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here.

scholarly journals New Type Direction Curves in 3-Dimensional Compact Lie Group

Symmetry ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 387 ◽  
Author(s):  
Ali Çakmak
Keyword(s):  
Lie Group ◽  
Three Dimensional ◽  
Normal Direction ◽  
General Definition ◽  
Compact Lie Group ◽  
3 Dimensional ◽  
New Type ◽  
Definition Of

In this paper, new types of associated curves, which are defined as rectifying-direction, osculating-direction, and normal-direction, in a three-dimensional Lie group G are achieved by using the general definition of the associated curve, and some characterizations for these curves are obtained. Additionally, connections between the new types of associated curves and the curves, such as helices, general helices, Bertrand, and Mannheim, are given.

scholarly journals Extension of the taxonomic coverage of the family GH126 outside Firmicutes and in silico characterization of its non-catalytic terminal domains

3 Biotech ◽  
2020 ◽  
Vol 10 (10) ◽  
Author(s):  
Lenka Kerényiová ◽  
Štefan Janeček
Keyword(s):  
In Silico ◽  
Homology Modelling ◽  
Family Members ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Glycoside Hydrolases ◽  
Modular Organization ◽  
Conserved Sequence ◽  
The Family

Abstract The family GH126 is a family of glycoside hydrolases established in 2011. Officially, in the CAZy database, it counts ~ 1000 sequences originating solely from bacterial phylum Firmicutes. Two members, the proteins CPF_2247 from Clostridium perfringens and PssZ from Listeria monocytogenes have been characterized as a probable α-amylase and an exopolysaccharide-specific glycosidase, respectively; their three-dimensional structures being also solved as possessing catalytic (α/α)6-barrel fold. Previously, based on a detailed in silico analysis, the seven conserved sequence regions (CSRs) were identified for the family along with elucidating basic evolutionary relationships within the family members. The present study represents a continuation study focusing on two particular aims: (1) to find out whether the taxonomic coverage of the family GH126 might be extended outside the Firmicutes and, if positive, to deliver those out-of-Firmicutes proteins with putting them into the context of the family; and (2) to identify the family members containing the N- and/or C-terminal extensions of their polypeptide chain, additional to the catalytic (α/α)6-barrel domain, and perform the bioinformatics characterization of the extra domains. The main results could be summarized as follows: (1) 17 bacterial proteins caught by BLAST searches outside Firmicutes (especially from phyla Proteobacteria, Actinobacteria and Bacteroidetes) have been found and convincingly suggested as new family GH126 members; and (2) a thioredoxin-like fold and various leucine-rich repeat motifs identified by Phyre2 structure homology modelling have been recognized as extra domains occurring most frequently in the N-terminal extensions of family GH126 members possessing a modular organization.

scholarly journals Extra-Ribosomal Functions of the Ribosomal Protein, RPS3 as Predicted by In Silico Analysis

1970 ◽  
Vol 4 (2) ◽  
pp. 62-69
Author(s):  
Edmund Ui-Hang Sim ◽  
Chin-Ming Er
Keyword(s):  
Ribosomal Protein ◽  
In Silico ◽  
Rna Splicing ◽  
De Novo ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Computational Prediction ◽  
Regulation Of Transcription ◽  
Functional Studies ◽  
In Silico Studies

Products of ribosomal protein (RP) genes have been found to play extra-ribosomal roles that range from DNA repair to RNA splicing. Their association with congenital disorders or cancers has also been widely documented. However, the relatively large number of different RPs, each with perhaps unique biological roles, has compounded the comprehensive elucidation of the physiological functions of each RPs. Experimental functional studies on the many and variegated RPs are labour intensive, time-consuming and costly. Moreover, experimental studies unguided by theoretically insights entail inaccurate results. Therefore, knowledge on the actual roles of these proteins remains largely undefined. A valid alternative is the use of bioinformatics resources to computationally predict functional roles of these biomolecules. Findings from such in silico studies of the RPS3 are reported herein. We reveal an array of possible extra-ribosomal functions that includes regulation of transcription (including via NF-κB-mediated, POK-induced and DNA-dependent), regulation of p53 activities and its stabilisation, inflammatory immune response, modulation of nNOS activities, and anti-oxidative capabilities. Our findings provide computational prediction of de novo extra-ribosomal functions of RPS3. These results will enhance the theoretical basis for designing future experimental studies on elucidating its definitive physiological roles.

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