Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants

Flooding is a natural disaster that causes considerable damage to different sectors and severely affects economic and social activities. The city of Saqqez in Iran is susceptible to flooding due to its specific environmental characteristics. Therefore, susceptibility and vulnerability mapping are essential for comprehensive management to reduce the harmful effects of flooding. The primary purpose of this study is to combine the Analytic Network Process (ANP) decision-making method and the statistical models of Frequency Ratio (FR), Evidential Belief Function (EBF), and Ordered Weight Average (OWA) for flood susceptibility mapping in Saqqez City in Kurdistan Province, Iran. The frequency ratio method was used instead of expert opinions to weight the criteria in the ANP. The ten factors influencing flood susceptibility in the study area are slope, rainfall, slope length, topographic wetness index, slope aspect, altitude, curvature, distance from river, geology, and land use/land cover. We identified 42 flood points in the area, 70% of which was used for modelling, and the remaining 30% was used to validate the models. The Receiver Operating Characteristic (ROC) curve was used to evaluate the results. The area under the curve obtained from the ROC curve indicates a superior performance of the ANP and EBF hybrid model (ANP-EBF) with 95.1% efficiency compared to the combination of ANP and FR (ANP-FR) with 91% and ANP and OWA (ANP-OWA) with 89.6% efficiency.

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“…where TN, FP, TP, and FN are true negative, false positive, true positive, and false negative (Leman et al 2020).…”

Section: Models Validationmentioning

confidence: 99%

Flood susceptibility mapping using an improved analytic network process with statistical models

Yariyan

Avand

Abbaspour

et al. 2020

Geomatics, Natural Hazards and Risk

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“…The branch point is located ~40 nucleotides upstream of the splice acceptor and is always an adenine. A number of exonic and intronic sequence elements, named exonic/intronic splicing enhancers (ESEs and ISEs) and exonic/intronic splicing silencers (ESSs and ISSs), influence the final splicing outcome 12–14 . Thus, variants in these conserved sequences could affect RNA expression levels by nonsense‐mediated mRNA decay (NMD), a translation‐coupled mechanism that eliminates mRNAs containing premature translation‐termination codons 15 …”

Section: Discussionmentioning

confidence: 99%

RNA and protein expression analysis of HLA‐DQB103:01:01:21Q* allele: A null allele renamed as HLA‐DQB103:01:01:21N*

Rubio¹,

Aroca‐Aguilar

Luis-Hidalgo

et al. 2022

HLA

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The characterization of the expression profile of HLA questionable alleles (Q) is clinically relevant in allogeneic hematopoietic stem cell transplantation (HSTC) because an aberrant expression of these alleles could lead to transplantation‐related complications. HLA‐DQB1*03:01:01:21Q shows a substitution at the donor splice site of intron 3 that potentially could affect the expression of this allele. In order to determine their expression profile at RNA and protein level, we analyzed the presence of the HLA‐DQ7 molecule by complement‐dependent cytotoxicity test (CDC) and flow cytometry, and their RNA processing by cDNA analyses and sequencing by Sanger methods. Our results reveal that HLA‐DQ7 is not detectable by serological methods, this is confirmed by cDNA methods demonstrating the absence of specific HLA‐DQB1*03:01:01:21Q mRNA, probably due to an intron 3 retention that creates a premature TGA stop codon, leading to mRNA degradation via nonsense‐mediated decay (NMD). These findings demonstrate that the HLA‐DQB1*03:01:01:21Q allele is nonexpressed, thus it has been renamed as DQB1*03:01:01:21N.

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“…48 Generating such novel data sets and increasing their number will undoubtedly contribute to refine algorithms and further improve the robustness as well as the accuracy of those tools. 49,50…”

Section: Relevance Of In Silico Prediction and Modeling Tools For Interpreting The Role Of Rare Variants In Geneticsmentioning

confidence: 99%

Missense RHD single nucleotide variants induce weakened D antigen expression by altering splicing and/or protein expression

et al. 2021

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Background Although D variant phenotype is known to be due to genetic defects, including rare missense single nucleotide variants (SNVs), within the RHD gene, few studies have addressed the molecular and cellular mechanisms driving this altered expression. We and others showed previously that splicing is commonly disrupted by SNVs in constitutive splice sites and their vicinity. We thus sought to investigate whether rare missense SNVs located in “deep” exonic regions could also impair this mechanism. Study design and methods Forty‐six missense SNVs reported within exons 6 and 7 were first selected from the Human RhesusBase. Their respective effect on splicing was assessed by using an in vitro assay. An RhD‐negative cell model was further generated by using the CRISPR‐Cas9 approach. RhD‐mutated proteins were overexpressed in the newly created model, and cell membrane expression of the D antigen was measured by flow cytometry. Results Minigene splicing assay showed that 14 of 46 (30.4%) missense SNVs alter splicing. Very interestingly, further investigation of two missense SNVs, which both affect codon 338 and confer a weak D phenotype, showed various mechanisms: c.1012C>G (p.Leu338Val) disrupts splicing only, while c.1013T>C (p.Leu338Pro) alters only the protein structure, in agreement with in silico prediction tools and 3D protein structure visualization. Conclusion Our functional data set suggests that missense SNVs damage quantitatively D antigen expression by, at least, two different mechanisms (splicing alteration and protein destabilization) that may act independently. These data thereby contribute to extend the current knowledge of the molecular mechanisms governing weakened D expression.

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Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants

Cited by 4 publications

References 30 publications

Flood susceptibility mapping using an improved analytic network process with statistical models

Flood susceptibility mapping using an improved analytic network process with statistical models

RNA and protein expression analysis of HLA‐DQB103:01:01:21Q* allele: A null allele renamed as HLA‐DQB103:01:01:21N*

Missense RHD single nucleotide variants induce weakened D antigen expression by altering splicing and/or protein expression

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Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants

Cited by 4 publications

References 30 publications

Flood susceptibility mapping using an improved analytic network process with statistical models

Flood susceptibility mapping using an improved analytic network process with statistical models

RNA and protein expression analysis of HLA‐DQB1*03:01:01:21Q allele: A null allele renamed as HLA‐DQB1*03:01:01:21N

Missense RHD single nucleotide variants induce weakened D antigen expression by altering splicing and/or protein expression

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RNA and protein expression analysis of HLA‐DQB103:01:01:21Q* allele: A null allele renamed as HLA‐DQB103:01:01:21N*