scholarly journals In Silico Analysis of Variants of Uncertain Significance in AP4S1 Gene

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Sobia Nazir Chaudry ◽  
Ammara Akhtar ◽  
Ayman Naeem ◽  
Dr. Mureed Husaain
Keyword(s):  
Splice Site ◽  
Protein Function ◽  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Low Frequency ◽  
In Silico Analysis ◽  
Neurological Complications ◽  
Lower Limbs ◽  
Spastic Paraplegia ◽  
Silico Analysis

Hereditary spastic paraplegia is a group of heterogeneous neurological disorders with genetic etiologies. It is characterized by spasticity in lower limbs along with neurological complications. Sequencing technologies have identified numerous disease causing variants in AP4S1 gene. However, many very low frequency variations in AP4S1 have the potential to cause hereditary spastic paraplegia in a recessive inheritance manner. This study was designed to identify these potential disease causing variants in AP4S1 gene using in silico tools. These tools predict the effects of deleterious variants on protein function and pre-mRNA splicing. To predict the pathogenicity of missense variants PhD-SNPg, PROVEAN, SNPs&GO, and CADD were used. Splice site variants were analyzed using Spliceman, SPiCE, and Human Splice Finder (HSF). In silico analysis identified six missense and five splice site variants with the potential to cause hereditary spastic paraplegia.

scholarly journals Genetics A Comprehensive In Silico Analysis of Deleterious SNPs of Paraplegin Protein Associated with Hereditary Spastic Paraplegia through Mitochondrial Dysfunction

2020 ◽  
Vol 2 (2) ◽  
pp. 1-14
Author(s):  
Ammara Akhtar ◽  
Sobia Nazir Choudhry ◽  
Rana Muhammad Mateen ◽  
Mureed Hussain
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Mitochondrial Protein ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Spastic Paraplegia ◽  
Bioinformatic Tools ◽  
Pathogenic Variants ◽  
Structural And Functional Properties ◽  
Silico Analysis

Hereditary spastic paraplegia (HSP) is a heterogenous neurological disorder primarily associated with progressive spasticity. Paraplegin is a mitochondrial protein and mutations in this protein can lead to HSP. In this study, in silico analysis was carried out to identify the pathogenic variants of SPG7 (paraplegin protein). To find novel pathogenic mutations, missense and splicing variants were collected from gnomAD database and passed through a detailed and stringent analysis with the help of a variety of bioinformatic tools. The list of mutations was examined and compared in ClinVar. Altogether, 14 missense mutations and 18 splicing mutations were obtained and these mutations were predicted to have the potential of disrupting the normal structural and functional properties of paraplegin protein.

scholarly journals Two novel variants in DYRK1B causative of AOMS3: expanding the clinical spectrum

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elvia C. Mendoza-Caamal ◽  
Francisco Barajas-Olmos ◽  
Elaheh Mirzaeicheshmeh ◽  
Ian Ilizaliturri-Flores ◽  
Carlos A. Aguilar-Salinas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Protein Function ◽  
In Silico ◽  
Metabolic Diseases ◽  
In Silico Analysis ◽  
Diagnostic Strategies ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Silico Analysis

Abstract Background We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. Results After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. Conclusions Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

scholarly journals Six splice site variations, three of them novel, in the ABO gene occurring in nine individuals with ABO subtypes

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaozhen Hong ◽  
Yanling Ying ◽  
Jingjing Zhang ◽  
Shu Chen ◽  
Xianguo Xu ◽  
...  
Keyword(s):  
Splice Site ◽  
In Silico ◽  
In Silico Analysis ◽  
Antigen Expression ◽  
Splice Sites ◽  
Serological Method ◽  
Typing Method ◽  
Allele Specific ◽  
Polymerase Chain ◽  
Silico Analysis

Abstract Background Nucleotide mutations in the ABO gene may reduce the activity of glycosyltransferase, resulting in lower levels of A or B antigen expression in red blood cells. Six known splice sites have been identified according to the database of red cell immunogenetics and the blood group terminology of the International Society of Blood Transfusion. Here, we describe six distinct splice site variants in individuals with ABO subtypes. Methods The ABO phenotype was examined using a conventional serological method. A polymerase chain reaction sequence-based typing method was used to examine the whole coding sequence of the ABO gene. The ABO gene haplotypes were studied using allele-specific primer amplification or cloning technology. In silico analytic tools were used to assess the functional effect of splice site variations. Results Six distinct variants in the ABO gene splice sites were identified in nine individuals with ABO subtypes, including c.28 + 1_2delGT, c.28 + 5G > A, c.28 + 5G > C, c.155 + 5G > A, c.204-1G > A and c.374 + 5G > A. c.28 + 1_2delGT was detected in an Aw individual, while c.28 + 5G > A, c.28 + 5G > C, and c.204-1G > A were detected in Bel individuals. c.155 + 5G > A was detected in one B3 and two AB3 individuals, whereas c.374 + 5G > A was identified in two Ael individuals. Three novel splice site variants (c.28 + 1_2delGT, c.28 + 5G > A and c.28 + 5G > C) in the ABO gene were discovered, all of which resulted in low antigen expression. In silico analysis revealed that all variants had the potential to alter splice transcripts. Conclusions Three novel splice site variations in the ABO gene were identified in Chinese individuals, resulting in decreased A or B antigen expression and the formation of ABO subtypes.

scholarly journals Extensive In Silico Analysis of ATL1 Gene : Discovered Five Mutations That May Cause Hereditary Spastic Paraplegia Type 3A

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mujahed I. Mustafa ◽  
Naseem S. Murshed ◽  
Abdelrahman H. Abdelmoneim ◽  
Miyssa I. Abdelmageed ◽  
Nafisa M. Elfadol ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Computational Analysis ◽  
3D Structure ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Structural Level ◽  
Spastic Paraplegia ◽  
Analysis Tools ◽  
The Impact

Background. Hereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP which is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. SPG3A gene mutations and the phenotype-genotype correlations have not yet been recognized. The aim of this work was to categorize the most damaging SNPs in ATL1 gene and to predict their impact on the functional and structural levels by several computational analysis tools. Methods. The raw data of ATL1 gene were retrieved from dbSNP database and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0 and MUPro, respectively, to investigate their effect on the structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids. Results. Five nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, and rs1242753115). Conclusions. In this study, the impact of nsSNPs in the ATL1 gene was investigated by various in silico tools that revealed five nsSNPs (V67F, T120I, R217Q, R495W, and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein and, therefore, can be used as genomic biomarkers specifically before 4 years of age; also, it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.

Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5′ splice-site disruption

2007 ◽  
Vol 28 (6) ◽  
pp. 599-612 ◽  
Author(s):  
K. Wimmer ◽  
X. Roca ◽  
H. Beiglböck ◽  
T. Callens ◽  
J. Etzler ◽  
...  
Keyword(s):  
Splice Site ◽  
In Silico ◽  
In Silico Analysis ◽  
Splicing Defects ◽  
Silico Analysis

A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma

2020 ◽  
Vol 47 (6) ◽  
pp. 398-408
Author(s):  
Sonam Tulsyan ◽  
Showket Hussain ◽  
Balraj Mittal ◽  
Sundeep Singh Saluja ◽  
Pranay Tanwar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gallbladder Carcinoma ◽  
In Silico ◽  
In Silico Analysis ◽  
Transcriptomic Profile ◽  
Silico Analysis

Enalos Suite of Tools: Enhancing Cheminformatics and Nanoinfor - matics through KNIME

2020 ◽  
Vol 27 (38) ◽  
pp. 6523-6535 ◽  
Author(s):  
Antreas Afantitis ◽  
Andreas Tsoumanis ◽  
Georgia Melagraki
Keyword(s):  
Data Analysis ◽  
Virtual Screening ◽  
In Silico ◽  
Model Development ◽  
In Silico Analysis ◽  
Material Design ◽  
Efficient Solutions ◽  
Biological Data ◽  
Cost Efficient ◽  
Silico Analysis

Drug discovery as well as (nano)material design projects demand the in silico analysis of large datasets of compounds with their corresponding properties/activities, as well as the retrieval and virtual screening of more structures in an effort to identify new potent hits. This is a demanding procedure for which various tools must be combined with different input and output formats. To automate the data analysis required we have developed the necessary tools to facilitate a variety of important tasks to construct workflows that will simplify the handling, processing and modeling of cheminformatics data and will provide time and cost efficient solutions, reproducible and easier to maintain. We therefore develop and present a toolbox of >25 processing modules, Enalos+ nodes, that provide very useful operations within KNIME platform for users interested in the nanoinformatics and cheminformatics analysis of chemical and biological data. With a user-friendly interface, Enalos+ Nodes provide a broad range of important functionalities including data mining and retrieval from large available databases and tools for robust and predictive model development and validation. Enalos+ Nodes are available through KNIME as add-ins and offer valuable tools for extracting useful information and analyzing experimental and virtual screening results in a chem- or nano- informatics framework. On top of that, in an effort to: (i) allow big data analysis through Enalos+ KNIME nodes, (ii) accelerate time demanding computations performed within Enalos+ KNIME nodes and (iii) propose new time and cost efficient nodes integrated within Enalos+ toolbox we have investigated and verified the advantage of GPU calculations within the Enalos+ nodes. Demonstration data sets, tutorial and educational videos allow the user to easily apprehend the functions of the nodes that can be applied for in silico analysis of data.

In-Silico Analysis of Chromone Containing Sulfonamide Derivatives as Human Carbonic Anhydrase Inhibitors

2013 ◽  
Vol 9 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Zaheer Ul-Haq ◽  
Saman Usmani ◽  
Uzma Mahmood ◽  
Mariya al-Rashida ◽  
Ghulam Abbas
Keyword(s):  
Carbonic Anhydrase ◽  
In Silico ◽  
In Silico Analysis ◽  
Carbonic Anhydrase Inhibitors ◽  
Human Carbonic Anhydrase ◽  
Silico Analysis
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