Biology subjects

Ikram, A.

Publications and source records attributed to Ikram, A..

11 recordsLinked to original sources

bioRxiv2024

Associations between common genetic variants and income provide insights about the socioeconomic health gradient

We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EAs genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.

genetics↗

bioRxiv2023

DEVELOPMENT AND EVALUATION OF COATED RICOTTA CHEESE WITH WHEY PROTEIN AND CLOVE OIL

Cheese, oldest dairy product which is used to preserve the nutrients of milk for long time. It is available in different shapes, sizes, flavors and textures. Ricotta is fresh soft cheese, is prepared through coagulating the whey proteins. It is a value-added product manufactured from cheese whey. Microbial spoiling occurs as a result of unmanaged conditions, resulting in the unfavorable changes in odor, flavor, and texture. That leads to food poisoning when infected food is consumed. Natural preservatives are preferred by consumers over synthetic preservatives since they are safer and extend the shelf life of food goods. Synthetic preservatives are poisonous and have negative health consequences. Edible coatings are biodegradable, natural films that can improve the products safety, quality, and nutritional content until it is consumed. This research was carried out to analyse the effect of whey protein and clove essential oil on the shelf life of ricotta cheese due to their excellent gas barrier properties, antioxidant and antimicrobial properties. Different concentrations of clove oil (0.1, 0.2, 0.3 %) are incorporated in whey protein coating solution (2.5,5,7.5%). The overall findings for all groups showed that there was gradual decrease in acidity and moisture content. Therefore, sample TRC3 treated with 0.75 % whey protein and 0.3% clove oil showed significant results (P<0.05). They showed less microbial count, increased fat and protein value. But it also had great impact on sensory analysis such as on color, texture, aroma while it showed significant overall acceptability due to high clove oil and whey protein concentrations. Hence, this study showed significant effect on shelf life of ricotta cheese and its shelf life increased from 7 to 21 days.

microbiology↗

bioRxiv2023

Computational insights on the destabilizing mutations in the binding site of 3CL-protease SARS-CoV-2 Omicron (VOC)

The COVID-19 (Corona Virus Disease 19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is causing enormous difficulties in the worlds economies and there is uncertainty as to whether the current prophylactic measures will offer adequate protection globally after the appearance of virus variants that like that indicated as Omicron emerged in the presence of global vaccine-based immunization. While several studies are available describing the main differences in the spike protein of Omicron compared to the other variants previously emerged, there was no structural insights into the 3CL-protease (3CLpro) associated to the new variant. Herein, we performed a computational study based on genomic data and amino acid sequences available in the most updated COVID-19-related databases that allowed us to build up in silico the 3D structure of Omicron 3CLpro. Moreover, by molecular dynamics simulation we demonstrated that currently available drugs acting as inhibitors of the SARS-CoV-2 main protease could be less effective in the case of Omicron variant due to the different chemical interactions in the binding site occurred after the recent amino acid mutations. Ultimately, our study highlights the need of exploiting in silico and in vitro methods to discover novel 3CLpro inhibitors starting from the computationally based structure we presented herein, and more in general to direct the major efforts to targeting the most conserved 3CLpro regions that appeared unchanged in the context of the Omicron variant.

bioinformatics↗

bioRxiv2023

In-silico Analysis of SARS-Cov2 Spike Proteins of Different Field Variants

BackgroundCoronaviruses belong to the group of RNA family of viruses which trigger diseases in birds, humans, and mammals, which can cause respiratory tract infections. The COVID-19 pandemic has badly affected every part of the world, and the situation in the world is getting worse with the emergence of novel variants. Our study aims to explore the genome of SARS-,CoV2 followed by in silico analysis of its proteins. MethodsDifferent nucleotide and protein variants of SARS-Cov2 were retrieved from NCBI. Contigs & consensus sequences were developed to identify variations in these variants by using SnapGene. Data of variants that significantly differ from each other was run through Predict Protein software to understand changes produced in protein structure The SOPMA web server was used to predict the secondary structure of proteins. Tertiary structure details of selected proteins were analyzed using the online web server SWISS-MODEL. FindingsSequencing results shows numerous single nucleotide polymorphisms in surface glycoprotein, nucleocapsid, ORF1a, and ORF1ab polyprotein. While envelope, membrane, ORF3a, ORF6, ORF7a, ORF8, and ORF10 genes have no or few SNPs. Contigs were mto identifyn of variations in Alpha & Delta Variant of SARs-CoV-2 with reference strain (Wuhan). The secondary structures of SARs-CoV-2 proteins were predicted by using sopma software & were further compared with reference strain of SARS-CoV-2 (Wuhan) proteins. The tertiary structure details of only spike proteins were analyzed through the SWISS-MODEL and Ramachandran plot. By Swiss-model, a comparison of the tertiary structure model of SARS-COV-2 spike protein of Alpha & Delta Variant was made with reference strain (Wuhan). Alpha & Delta Variant of SARs-CoV-2 isolates submitted in GISAID from Pakistan with changes in structural and nonstructural proteins were compared with reference strain & 3D structure mapping of spike glycoprotein and mutations in amino acid were seen. ConclusionThe surprising increased rate of SARS-CoV-2 transmission has forced numerous countries to impose a total lockdown due to an unusual occurrence. In this research, we employed in silico computational tools to analyze SARS-CoV-2 genomes worldwide to detect vital variations in structural proteins and dynamic changes in all SARS-CoV-2 proteins, mainly spike proteins, produced due to many mutations. Our analysis revealed substantial differences in functional, immunological, physicochemical, & structural variations in SARS-CoV-2 isolates. However real impact of these SNPs can only be determined further by experiments. Our results can aid in vivo and in vitro experiments in the future.

bioinformatics↗

bioRxiv2022

Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus

Biogeographic variations in the gut microbiota reflect host and environmental factors delineating human populations, and are pivotal to understand global patterns of host-microbiota interactions in health and prevalent lifestyle-related diseases, such as type 2 diabetes mellitus (T2D). Pakistani adults, having an exceptionally high prevalence of T2D, are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by 16S ribosomal RNA gene amplicon sequencing and qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis. Overall, urbanized Pakistanis gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.

microbiology↗

bioRxiv2022

Genomic Characterization of Sars-Cov-2 from Islamabad Pakistan by Rapid Nanopore Sequencing

Since the start of COVID-19 pandemic, Pakistan has experienced four waves of pandemic. The fourth wave ended in October, 2021 while the fifth wave of pandemic starts in January, 2022. The data regarding the circulating strains after the fourth wave of pandemic from Pakistan is not available. The current study explore the genomic diversity of SARS-CoV-2 after fourth wave and before fifth wave of pandemic through whole genome sequencing. The results showed the circulation of different strains of SARS-CoV-2 during November-December, 2021. We have Omicron BA.1 (n=4), Lineage A (n=2) and delta AY.27 (n=1) variants of SARS-CoV-2 in the population of Islamabad. All the isolates harbors characteristics mutations of omicron and delta variant in the genome. The lineage A isolate harbors a nine amino acid (68-76) and a ten amino acid (679-688) deletion in the genome. The circulation of omicron in the population before the fifth wave of pandemic and subsequent upsurges of COVID-19 positive cases in Pakistan highlights the importance of genomic surveillance.

molecular biology↗

bioRxiv2021

A Computational Dissection of Spike protein of SARS-CoV-2 Omicron Variant

The emergence of SARS-CoV-2 omicron variant in late November, 2021 and its rapid spread to different countries, warns the health authorities to take initiative to work on containing its spread. The omicron SARS-CoV-2 variant is unusual from the other variants of concerns reported earlier as it harbors many novel mutations in its genome particularly with >30 mutations in the spike glycoprotein alone. The current study investigated the variation in binding mechanism which it carries compared to the wild type. The study also explored the interaction profile of spike-omicron with human ACE2 receptor. The structure of omicron spike glycoprotein was determined though homology modeling. The interaction analysis was performed through docking using HADDOCK followed by binding affinity calculation. Finally, the comparison of interactions were performed among spike-ACE2 complex of wild type, delta and omicron variants. The interaction analysis has revealed the involvement of highly charged and polar residues (H505, Arg498, Ser446, Arg493, and Tyr501) in the interactions. The important novel interactions in the spike-ACE2-omicron complex was observed as S494:H34, S496:D38, R498:Y41, Y501:K353, and H505:R393 and R493:D38. Moreover, the binding affinity of spike-ACE2-omicron complex (-17.6Kcal/mol) is much higher than wild type-ACE2 (-13.2Kcal/mol) and delta-ACE2 complex (-13.3Kcal/mol). These results indicate that the involvement of polar and charged residues in the interactions with ACE2 may have an impact on increased transmissibility of omicron variant.

bioinformatics↗

bioRxiv2021

The impact of mutations on the structural and functional properties of SARS-CoV-2 proteins: A comprehensive bioinformatics analysis

An in-depth analysis of first wave SARS-CoV-2 genome is required to identify various mutations that significantly affect viral fitness. In the present study, we have performed comprehensive in-silico mutational analysis of 3C-like protease (3CLpro), RNA dependent RNA polymerase (RdRp), and spike (S) proteins with the aim of gaining important insights into first wave virus mutations and their functional and structural impact on SARS-CoV-2 proteins. Our integrated analysis gathered 3465 SARS-CoV-2 sequences and identified 92 mutations in S, 37 in RdRp, and 11 in 3CLpro regions. The impact of those mutations was also investigated using various in silico approaches. Among these 32 mutations in S, 15 in RdRp, and 3 in 3CLpro proteins are found to be deleterious in nature and could alter the structural and functional behavior of the encoded proteins. D614G mutation in spike and P323L in RdRp are the globally dominant variants with a high frequency. Most of them have also been found in the binding moiety of the viral proteins which determine their critical involvement in the host-pathogen interactions and drug targets. The findings of the current study may facilitate better understanding of COVID-19 diagnostics, vaccines, and therapeutics.

bioinformatics↗

bioRxiv2020

Development Optimization and Validation of RT-LAMP based COVID-19 Facility in Pakistan

The pandemic SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has created a widespread panic across the globe especially in the developing countries like Pakistan. The lack of resources and technical staff are causing havoc challenges in the detection and prevention of this global outbreak. Therefore, a less expensive and massive screening of suspected individuals for COVID-19 is required. In this study, a user-friendly technique of reverse transcription-loop mediated isothermal amplification (RT-LAMP) was designed and validated to suggest a potential RT-qPCR alternate for rapid testing of COVID-19 suspected individuals. A total of 12 COVID-19 negative and 72 COVID-19 suspected individuals were analyzed. Both RT-qPCR and RT-LAMP assays were performed for all the individuals using open reading frame (ORF 1ab), nucleoprotein (N) and Spike (S) genes. All 12 specimens which were negative using RT-qPCR were also found negative using RT-LAMP assay. Overall 62 out of 72 positive samples (detected using RT-qPCR) were found COVID-19 positive using RT-LAMP assay. Interestingly all samples (45) having Ct values less than 30 showed 100% sensitivity. However, samples with weaker Ct values (i.e., => 35) showed 54% concordance, suggesting potential false negatives or false positives in RT-LAMP or RT-qPCR results, respectively. Overall comparative assessment showed that RT-LAMP assay showed strong sensitivity and specificity and can be used as an alternative strategy for rapid COVID-19 testing. Hence, based on fast processing time, minimal risk of specimens transfer and utilizing available resources, LAMP based detection of COVID-19 is strongly advocated especially for developing countries.

molecular biology↗

bioRxiv2019

Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics

Background and aimMost patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. MethodsThe low incidence rate complicates prospective biomarker studies. Here, we took advantage of the availability of biobanked samples from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian biobank, Rotterdam Study) and identified prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between one month and seventeen years after blood sampling, and compared these with age- and gender-matched controls from the same cohorts. We applied 1H-NMR-based metabolomics on the Nightingale platform on these samples and applied logistic regression to assess the predictive value of individual metabolite concentrations, with gender, age, body mass index, smoking status, type 2 diabetes mellitus status, fasting status, and cohort as covariates. ResultsAfter quality assessment, we retained 356 cases and 887 controls. We identified two interesting hits, glutamine (p=0.011) and histidine (p=0.012), and obtained Westfall-Young family-wise error rate adjusted p-values of 0.43 for both. Stratification in quintiles showed a 1.5x elevated risk for the lowest 20% of glutamine and a 2.2x increased risk for the lowest 20% of histidine. Stratification by time to diagnosis (<2 years, 2-5 years, >5 years) suggested glutamine to be involved in an earlier process, tapering out closer to onset, and histidine in a process closer to the actual onset. Lasso-penalized logistic regression showed a slight improvement of the area under the Receiver Operator Curves when including glutamine and histidine in the model. Finally, our data did not support the earlier identified branched-chain amino acids as potential biomarkers for pancreatic cancer in several American cohorts. ConclusionWhile identifying glutamine and histidine as early biomarkers of potential biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.

epidemiology↗

bioRxiv2018

High-dimensional mapping of cognition to the brain using voxel-based morphometry and subcortical shape analysis.

BackgroundIt is increasingly recognized that the complex functions of human cognition are not accurately represented by arbitrarily-defined anatomical brain regions. Given the considerable functional specialization within such regions, more fine-grained studies of brain structure could capture such localized associations. However, such analyses/studies in a large community-dwelling population are lacking.\n\nMethodsIn 3,813 stroke-free and non-demented persons from the Rotterdam Study (mean age 69.1 ({+/-}8.8) years; 55.8% women) with cognitive assessments and brain MRI, we performed voxel-based morphometry and subcortical shape analysis on global cognition and separate tests that tapped into memory, information processing speed, fine motor speed, and executive function domains.\n\nResultsWe found that the different cognitive tests significantly associated with grey matter voxels in differential but also overlapping brain regions, primarily in the left hemisphere. Clusters of significantly associated voxels with global cognition were located within multiple anatomic regions: left amygdala, hippocampus, parietal lobule, superior temporal gyrus, insula and posterior temporal lobe. Subcortical shape analysis revealed associations primarily within the head and tail of the caudate nucleus, putamen, ventral part of the thalamus, and nucleus accumbens, more equally distributed among the left and right hemisphere. Within the caudate nucleus both positive (head) as well as negative (tail) associations were observed with global cognition.\n\nConclusionsIn a large population-based sample, we mapped cognitive performance to (sub)cortical grey matter using a hypothesis-free approach with high-dimensional neuroimaging. Leveraging the power of our large sample size, we confirmed well-known associations as well as identified novel brain regions related to cognition.

neuroscience↗