Computational prediction of phosphorylation sites of SARS-CoV-2 infection using feature fusion and optimization strategies.

SARS-CoV-2's global spread has instigated a critical health and economic emergency, impacting countless individuals. Understanding the virus's phosphorylation sites is vital to unravel the molecular intricacies of the infection and subsequent changes in host cellular processes. Several computational methods have been proposed to identify phosphorylation sites, typically focusing on specific residue (S/T) or Y phosphorylation sites. Unfortunately, current predictive tools perform best on these specific residues and may not extend their efficacy to other residues, emphasizing the urgent need for enhanced methodologies. In this study, we developed a novel predictor that integrated all the residues (STY) phosphorylation sites information. We extracted ten different feature descriptors, primarily derived from composition, evolutionary, and position-specific information, and assessed their discriminative power through five classifiers. Our results indicated that Light Gradient Boosting (LGB) showed superior performance, and five descriptors displayed excellent discriminative capabilities. Subsequently, we identified the top two integrated features have high discriminative capability and trained with LGB to develop the final prediction model, LGB-IPs. The proposed approach shows an excellent performance on 10-fold cross-validation with an ACC, MCC, and AUC values of 0.831, 0.662, 0.907, respectively. Notably, these performances are replicated in the independent evaluation. Consequently, our approach may provide valuable insights into the phosphorylation mechanisms in SARS-CoV-2 infection for biomedical researchers.

Investigation and drug design for novel molecules from natural products as inhibitors for controlling multiple myeloma disease using in-silico tools.

Multiple myeloma (MM) is a disease that causes plasma cell growth in the bone marrow and immune globulin buildup in blood and urine. Despite recent advances in MM therapy, many still die due to its high mortality rate. A study using computational simulations analyzed 100 natural ingredients from the SANC database to determine if they inhibited the IgH domain, a known cause of multiple myeloma. Natural component Diospyrin inhibited the IgH enzyme with the best binding energy of -10.3 kcal/mol and three carbon-hydrogen bonds, followed by Parviflorone F complex with a binding energy of -10.1 kcal/mol and two conventional-hydrogen bonds. As a result, the Molecular Dynamic simulation was used to test the stability of the two complexes. During the simulation, the Diospyrin molecule dissociated from the protein at roughly 67.5 ns, whereas the Parviflorone F molecule stayed attached to the protein throughout. The latter was the subject of the investigation. The analysis of the production run data revealed that the Parviflorone F molecule exhibits a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The analysis of the production run data revealed that the Parviflorone F molecule exhibited a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The root mean square deviation (RMSD) plots for both the protein and complex showed a stable and steady average value of 4.4 Å for the first 82 nanoseconds of manufacture. As a result, the average value increased to 8.3 Å. Furthermore, the components of the binding free energy, as computed by MM-GBSA, revealed that the mean binding energy of the Parviflorone F molecule was -23.88 kcal/mol. Finally, after analyzing all of the examination data, Parviflorone F was identified as a powerful inhibitor of the IgH domain and hence of the MM disease, which requires further in-vivo conformation.Communicated by Ramaswamy H. Sarma.

Early Fruit Development Regulation-Related Genes Concordantly Expressed with TCP Transcription Factors in Tomato (Solanum lycopersicum).

The tomato (Solanum lycopersicum L.) is considered one of the most important vegetable crops globally, both agronomically and economically; however, its fruit development regulation network is still unclear. The transcription factors serve as master regulators, activating many genes and/or metabolic pathways throughout the entire plant life cycle. In this study, we identified the transcription factors that are coordinated with TCP gene family regulation in early fruit development by making use of the high-throughput sequencing of RNA (RNAseq) technique. A total of 23 TCP-encoding genes were found to be regulated at various stages during the growth of the fruit. The expression patterns of five TCPs were consistent with those of other transcription factors and genes. There are two unique subgroups of this larger family: class I and class II TCPs. Others were directly associated with the growth and/or ripening of fruit, while others were involved in the production of the hormone auxin. Moreover, it was discovered that TCP18 had an expression pattern that was similar to that of the ethylene-responsive transcription factor 4 (ERF4). Tomato fruit set and overall development are under the direction of a gene called auxin response factor 5 (ARF5). TCP15 revealed an expression that was in sync with this gene. This study provides insight into the potential processes that help in acquiring superior fruit qualities by accelerating fruit growth and ripening.

Composition of the gut microbiota in patients with inflammatory bowel disease in Saudi Arabia: A pilot study.

Conclusions: The results of this study provide an overview of the variations in microbiota diversity present in Saudi IBD patients compared to healthy controls. Results: The key finding was three negative bacterial biomarkers, Paraprevotellaceae, the Muribaculaceae families of Bacteroidetes phylum, and the Leuconostocaceae family of Firmicutes phylum, which had a higher relative abundance in healthy individuals compared to IBD patients. It was also found that primary microbiota signatures at certain genera and species levels, including Prevotella copri, Bifidobacterium adolescentis, Ruminococcus callidus, Coprococcus sp., Ruminococcus gnavus, Dorea formicigenerans, Leuconostoc, Dialister, Catenibacterium, Eubacterium biforme, and Lactobacillus mucosae, were absent in almost all IBD patients, while Veillonella dispar was absent in all healthy individuals. Methods: After obtaining an informed consent, fecal samples were collected from 11 participants with IBD (patients) and 10 healthy individuals (controls). The bacterial components of the microbial population were identified by next-generation sequencing of partial 16S rRNA. Statistically significant dissimilarities were observed between samples for all metrics. Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition attributed to a complex interaction between imbalances in the gut microbiome, environmental conditions, and a deregulated immune response. The aim of the study was to investigate the composition of the gut microbiome of Saudi patients with IBD.

Pharmacophore-based virtual screening approaches to identify novel molecular candidates against EGFR through comprehensive computational approaches and in-vitro studies.

Alterations to the EGFR (epidermal growth factor receptor) gene, which primarily occur in the axon 18-21 position, have been linked to a variety of cancers, including ovarian, breast, colon, and lung cancer. The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. These drugs are becoming less effective in EGFR targeted cancer treatment and developing resistance to cancer cell eradication, which sometimes necessitates stopping treatment due to the side effects. One in silico study has been conducted to identify EGFR antagonists using other compounds, databases without providing the toxicity profile, comparative analyses, or morphological cell death pattern. The goal of our study was to identify potential lead compounds, and we identified seven compounds based on the docking score and four compounds that were chosen for our study, utilizing toxicity analysis. Molecular docking, virtual screening, dynamic simulation, and in-vitro screening indicated that these compounds' effects were superior to those of already marketed medication (gefitinib). The four compounds obtained, ZINC96937394, ZINC14611940, ZINC103239230, and ZINC96933670, demonstrated improved binding affinity (-9.9 kcal/mol, -9.6 kcal/mol, -9.5 kcal/mol, and -9.2 kcal/mol, respectively), interaction stability, and a lower toxicity profile. In silico toxicity analysis showed that our compounds have a lower toxicity profile and a higher LD50 value. At the same time, a selected compound, i.e., ZINC103239230, was revealed to attach to a particular active site and bind more tightly to the protein, as well as show better in-vitro results when compared to our selected gefitinib medication. MTT assay, gene expression analysis (BAX, BCL-2, and ß-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC50 value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549.

CRISPR-based systems for sensitive and rapid on-site COVID-19 diagnostics.

The COVID-19 pandemic has strained healthcare systems. Sensitive, specific, and timely COVID-19 diagnosis is crucial for effective medical intervention and transmission control. RT-PCR is the most sensitive/specific, but requires costly equipment and trained personnel in centralized laboratories, which are inaccessible to resource-limited areas. Antigen rapid tests enable point-of-care (POC) detection but are significantly less sensitive/specific. CRISPR-Cas systems are compatible with isothermal amplification and dipstick readout, enabling sensitive/specific on-site testing. However, improvements in sensitivity and workflow complexity are needed to spur clinical adoption. We outline the mechanisms/strategies of major CRISPR-Cas systems, evaluate their on-site diagnostic capabilities, and discuss future research directions.

Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients.

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

The composition and stability of the vaginal microbiome of healthy women.

Our knowledge of the composition of the vaginal environment in healthy women stands greatly improved. An imbalance in microbial communities is associated with a number of different diseases, disorders and other adverse health outcomes. Cultivation-independent studies have been published indicating that each woman has unique vaginal microbiota. The vaginal microbiome in pregnant women is more stable and associated with high level of Lactobacillus, particularly, Lactobacillus crispatus and low bacterial diversity. The current review was planned to provide a more complete picture of the abundance of various bacteria species in the vagina and how they impact women's reproductive health and pregnancy outcomes. This should provide a better understanding of what is considered a "healthy" or "unhealthy" vaginal microbiome and how the dysibiosis of the vagina affects the women. Additionally, it was planned to identify factors that influence the structure and / or composition of the microbial community.

Gut microbiome skin axis in the development of atopic dermatitis.

Atopic dermatitis mostly starts with children in early life. Besides the aetiological factors, like environmental, dietary or medical exposures, gut-skin axis microbiome studies have an impact to investigate and to understand the relation between the gut microbiome and changes to the skin microbiom as well as resulting skin diseases like atopic dermatitis. Infants start forming their microbiome in early life and some studies suggest that this phase has a crucial role in AD development. Balanced bacterial composition is important to maintain healthy skin as the gut microbiome dysbiosis may result in dramatic shifting in the skin microbiome that gives better chance for some bacteria, such as staphylococcus aureus, to prevail which has been reported to contribute to AD development. Among several factors, immunological activity has a strong relation to microbiome, changed composition and AD development. Supplements of prebiotic and probiotic could be a positive treatment approach. More studies regarding the gut-skin axis microbiome in general and diseases associated with microbiome, such as AD, are needed.

Transcriptional analysis of Rhazya stricta in response to jasmonic acid

BACKGROUND: Jasmonic acid (JA) is a signal transducer molecule that plays an important role in plant development and stress response; it can also efficiently stimulate secondary metabolism in plant cells. RESULTS: RNA-Seq technology was applied to identify differentially expressed genes and study the time course of gene expression in Rhazya stricta in response to JA. Of more than 288 million total reads, approximately 27% were mapped to genes in the reference genome. Genes involved during the secondary metabolite pathways were up- or downregulated when treated with JA in R. stricta. Functional annotation and pathway analysis of all up- and downregulated genes identified many biological processes and molecular functions. Jasmonic acid biosynthetic, cell wall organization, and chlorophyll metabolic processes were upregulated at days 2, 6, and 12, respectively. Similarly, the molecular functions of calcium-transporting ATPase activity, ADP binding, and protein kinase activity were also upregulated at days 2, 6, and 12, respectively. Time-dependent transcriptional gene expression analysis showed that JA can induce signaling in the phenylpropanoid and aromatic acid pathways. These pathways are responsible for the production of secondary metabolites, which are essential for the development and environmental defense mechanism of R. stricta during stress conditions. CONCLUSIONS: Our results suggested that genes involved in flavonoid biosynthesis and aromatic acid synthesis pathways were upregulated during JA stress. However, monoterpenoid indole alkaloid (MIA) was unaffected by JA treatment. Hence, we can postulate that JA plays an important role in R. stricta during plant development and environmental stress conditions.

Dysbiosis of gut microbiota in inflammatory bowel disease: Current therapies and potential for microbiota-modulating therapeutic approaches.

There is a growing body of evidence reinforcing the unique connections between the host microbiome, health, and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn's disease, (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life, and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints.

Identification of Causative Variants Contributing to Nonsyndromic Orofacial Clefts Using Whole-Exome Sequencing in a Saudi Family.

Objectives: Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and palate. To identify the potential candidate genes contributing to polygenic diseases such as NSOFC, linkage analyses, genome-wide association studies, and genomic rearrangements can be used. Genomic analyses, based on massively parallel next-generation sequencing technologies, play a vital role in deciphering the genetic bases of NSOFCs. Materials and Methods: In this study, whole exome sequencing was employed to detect genes that likely contributed to the NSOFC phenotype in a consanguineous Saudi family. Results: The exome analysis revealed NRP1 (rs35320960) as one potential candidate gene that is involved in bone differentiation. The RPL27A gene (rs199996172), which plays a crucial role in ribosome biogenesis, also passed all filters to serve as a candidate gene for NSOFC in this family. Rare variants are situated within the 5' UTR of these two genes. Conclusion: The study suggests that rare variants in NRP1 and RPL27A may be associated with NSOFC disease etiology.

Identification of Genetic Variants Associated With Myocardial Infarction in Saudi Arabia.

The genetic variants associated with various genetic disorders have not been identified decisively in Saudi Arabia. Among these variants, six known for their association with coronary artery disease or myocardial infarction (MI) were studied on Saudi patients. Reference single nucleotide polymorphisms (SNPs) of these variants are rs5174, rs11591147, rs2259816, rs111245230, rs3782886 and rs2259820, referring to genes LRP8, PCSK9, HNF1A, SVEP1, BRAP and HNF1A, respectively. The analysis employed polymerase chain reaction panel coupled with mini-sequencing (SNapShot multiplex system) in order to identify these variants. A total of 100 MI patients and 103 healthy control individuals participated in this study. The six variants (SNPs) were evaluated for the risk of developing MI in the Saudi patients. Analysis of allele frequencies indicated that A allele of rs11591147 variant can be a protective allele, thus, is associated with the decreased risk of MI in Saudi individuals. Rare allele of rs111245230 variant (e.g., C allele) was extremely reduced, while rare allele of rs3782886 variant (e.g., G allele) does not exist in the ethnic signature of the Saudi population. This study elucidates the possible prediction of risk factors associated with severe diseases in Saudi population utilizing SNapShot multiplex system.

Molecular evolution of cytochrome C oxidase-I protein of insects living in Saudi Arabia.

The study underpins barcode characterization of insect species collected from Saudi Arabia and explored functional constraints during evolution at the DNA and protein levels to expect the possible mechanisms of protein evolution in insects. Codon structure designated AT-biased insect barcode of the cytochrome C oxidase I (COI). In addition, the predicted 3D structure of COI protein indicated tyrosine in close proximity with the heme ligand, depicted substitution to phenylalanine in two Hymenopteran species. This change resulted in the loss of chemical bonding with the heme ligand. The estimated nucleotide substitution matrices in insect COI barcode generally showed a higher probability of transversion compared with the transition. Computations of codon-by-codon nonsynonymous substitutions in Hymenopteran and Hemipteran species indicated that almost half of the codons are under positive evolution. Nevertheless, codons of COI barcode of Coleoptera, Lepidoptera and Diptera are mostly under purifying selection. The results reinforce that codons in helices 2, 5 and 6 and those in loops 2-3 and 5-6 are mostly conserved and approach strong purifying selection. The overall results argue the possible evolutionary position of Hymenopteran species among those of other insects.

Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes.

BACKGROUND: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D. METHODS: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC. RESULTS: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely "glucagon signaling", "glycine, serine and threonine" and "bile secretion". Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study. CONCLUSION: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.

Control of ß-sitosterol biosynthesis under light and watering in desert plant Calotropis procera.

Most scientific studies on Calotropis procera refer to the plant as an important source of pharmaceutical compounds and its valuable benefits in medicine. One of the most important substances in this plant is the potential immunostimulant ß-sitosterol (BS) that acts in improving human health. This study focused on the effects of lighting before and after irrigation on the BS accumulation pathway namely steroid biosynthesis. Studying the enzymes in BS biosynthetic pathway indicated the upregulation at dawn and predusk of the SMT2 and SMO2 genes encoding sterol methyltransferase 2 and methylsterol monooxygenase, two key enzymes in BS accumulation in C. procera. The results almost indicated no regulation at the different time points of the CYP710A gene encoding sterol 22-desaturase, an enzyme that acts in depleting ß-sitosterol towards the biosynthesis of stigmasterol. RNA-Seq data was validated via quantitative RT-PCR and results were positive. The data of ultra-performance liquid chromatography-tandem mass spectrometry analysis with regard to BS accumulation also aligned with those of RNA-Seq analysis. We focused on the effects of light before and after watering on BS accumulation in C. procera. Our results show that BS accumulation is high at dawn in both dehydrated and well-watered condition. While, the BS was dramatically decrease at midday in well-watered plants. This increase/decrease in BS content is correlated with rates of expression of SMT 2 gene. This gene is a key convertor between the different branches in the cardiac glycoside biosynthesis. Accordingly, it could be suggested that BS (or one of the descendent product) may play an important role in C. procera tolerance to drought/light intensity conditions.

Stepwise response of MeJA-induced genes and pathways in leaves of C. roseus.

Catharanthus roseus is a perennial herb known for the production of important terpenoid indole alkaloids (TIAs) in addition to a variety of phenolic compounds. The goal of the present work was to detect the prolonged effects of MeJA (6 uM) treatment across time (up to 24 days) in order to detect the stepwise response of MeJA-induced genes and pathways in leaves of C. rouses. Prolonged exposure of plants to MeJA (6 uM) treatment for different time points (6, 12 and 24 days) indicated that genes in the indole alkaloid biosynthesis pathway and upstream pathways were triggered earlier (e.g., 6 days) than those in the anthocyanin biosynthesis pathway and its upstream pathways (e.g., 12 days). Three enzymes, e.g., T16H, OMT, and D4H, in the six-step vindoline biosynthesis and two enzymes, e.g., TDC and STR, acting consecutively in the conversion of tryptophan to strictosidine, were activated after 6 days of MeJA treatment. Two other key enzymes, e.g., TRP and CYP72A1, acting concurrently upstream of the TIA biosynthesis pathway were upregulated after 6 days. The genes encoding TDC and STR might concurrently act as a master switch of the TIA pathway towards the production of the indole alkaloids. On the other hand, we speculate that the gene encoding PAL enzyme also acts as the master switch of phenylpropanoid biosynthesis and the downstream flavonoid biosynthesis and anthocyanin biosynthesis pathways towards the production of several phenolic compounds. PAL and the downstream enzymes were activated 12 days after treatment. Cluster analysis confirmed the concordant activities of the flower- and silique-specific bHLH25 transcription factor and the key enzyme in the TIA biosynthesis pathway, e.g., STR. Due to the stepwise response of the two sets of pathways, we speculate that enzymes activated earlier likely make TIA biosynthesis pathway a more favourable target in C. roseus than anthocyanin biosynthesis pathway.

Multifunctional activities of ERF109 as affected by salt stress in Arabidopsis.

Transcriptomic analysis was conducted in leaves of Arabidopsis T-DNA insertion ERF109-knocked out (KO) mutant or plants overexpressing (OE) the gene to detect its role in driving expression of programmed cell death- (PCD-) or growth-related genes under high salt (200 mM NaCl) stress. The analysis yielded ~22-24 million reads, of which 90% mapped to the Arabidopsis reference nuclear genome. Hierarchical cluster analysis of gene expression and principal component analysis (PCA) successfully separated transcriptomes of the two stress time points. Analysis indicated the occurrence of 65 clusters of gene expression with transcripts of four clusters differed at the genotype (e.g., WT (wild type), KO ERF109 or OE ERF109 ) level. Regulated transcripts involved DIAP1-like gene encoding a death-associated inhibitor of reactive oxygen species (ROS). Other ERF109-regulated transcripts belong to gene families encoding ROS scavenging enzymes and a large number of genes participating in three consecutive pathways, e.g., phenylalanine, tyrosine and tryptophan biosynthesis, tryptophan metabolism and plant hormone signal transduction. We investigated the possibility that ERF109 acts as a "master switch" mediator of a cascade of consecutive events across these three pathways initially by driving expression of ASA1 and YUC2 genes and possibly driving GST, IGPS and LAX2 genes. Action of downstream auxin-regulator, auxin-responsive as well as auxin carrier genes promotes plant cell growth under adverse conditions.

In Silico Approach to Investigate the Structural and Functional Attributes of Familial Hypercholesterolemia Variants Reported in the Saudi Population.

Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia (SA). FH is underreported and underdiagnosed in SA with statistical evidence of high expected prevalence in such a consanguineous community. Lacking knowledge of which and how these alterations are actually impacting lipid metabolism is one of the main reasons why FH is insufficiently diagnosed in the region. The aim of this study was to develop a fast prediction approach using an integrated bioinformatics method for future screening of the potential causative variants from national registries. A total of 21 variants were detected with majority rate in LDLR (81%). Variants were classified based on the type of mutation. Missense variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant analysis. Furthermore, functional interaction deformities showed a significant loss and gain of energies in the mutated proteins. These findings will help in distinguishing the most harmful mutations needed to be screened for clinically diagnosed FH patients in SA. Such computational research is necessary to avoid time consumption and the usage of expensive biological experiments. This can be a fast track to facilitate the future filtering and screening of causative mutations from national registries.