2023

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A Meta-Analysis of GWAS and Random effect model to detect novel loci in Atriai Fibrillation
(UMT, Lhr, 2023-10) Zunara Arshad
To find novel loci with atrial fibrillation risk variants, we undertake a large-scale metaanalysis of atrial fibrillation genome-wide association studies with over 19,166 atrial fibrillation cases and over 2,62,516 control people of European and Japanese ancestry Using the GWAS summary statistics we performed meta-analysis and applied random effect model over million SNPs and find out 1718 novel SNPs from which 15 SNPsarestrongly linked with Atrial Fibrillation (AF) . Risk loci of these 15 novel SNPs are KCNN3, SPATS2L, PHLDB2, PITX2, HNRNPAO, RNU1-18P, CAVl, AOPEP, NEURLl, KCNJ5, TBX5, SYNE2, HCN4, and ZFHX3 identified by using NCBI database. The novel SNPs located at 2q33.1, 4q25, 7q31.2, 10q24.33, 12q24.21 and 16q22.3 have p<5E-8 and shows highest peaks in the Manhattan plot indicating those risk variants that are most susceptible to AF in European and Japsinese population. The variants identified needs to be verified in independent case controls studied across different ethnicities
Assessment of thyroid dysfunction in type 2 diabetes mellitus
(UMT, Lhr, 2023) Abeera Asad
Thyroid gland is mostvital endocrine gland which regulates various body functions including metabolic functions, growth and development. Diabetes mellitus and thyroid dysfunction are prevalent and most common endocrines disorders among general population. The aim of our study is to determine thyroid dysfunction in type 2 diabetes by analyzing the level of thyroid hormones T3, T4, thyroid stimulating hormone and the lipid profile that includes serum total cholesterol, serum LDL, serum HDL cholesterol and triglycerides in type 2 diabetic patients and correlation between glucose fasting and random with thyroid hormonesT3, T4, TSH and lipid profile. The result of our research explores the levels of T3 that was found 102.95 while Thyroxine 4 hormone was 7.64 and level of TSH was2.3. The mean values for fasting Blood glucose level of patients was 114.99 and blood glucose random mean is 143.43.In whole population, the total serum cholesterol was190.03, the serum HDL cholesterol was 40.57.Blood Glucose fasting was analyzed by t-test with all other parameters to check that blood glucose fasting is related to T3, T4, TSH, LDL, HDL, Total Cholesterol and Triglycerides. All mentioned parameters correlation was non-significant (p>0.05)except Triglyceride with the p value (<0.05)0.000959014 which is significant and shows that increased blood glucose levels can increase triglyceride or there is a significant relation between these two. Blood Glucose random was also analyzed by t-test with all other parameters to check that blood glucose random is related to T3, T4, TSH, LDL, HDL, Total Cholesterol and Triglycerides. All parameters were non-significant with p-value (<0.05) except T3 with the p-value (<0.05) 0.0063 and with Total cholesterol levels with p-value 0.0024 which is significant which shows that increased blood glucose level has a relation with increased T3 and total cholesterol levels or there is a significant relation between these two. The conclusion of our study is that glucose level in diabetic patient with thyroid dysfunction affects lipid profile and positive correlation was found between glucose level and total cholesterol and triglycerides.
Bacterial augmented floating treatment wetlands for the remediation of paper mill effluent
(UMT, Lhr, 2023) Imran Liaqat
Paper industries play an important role in the world’s economy. The paper industry generates a huge amount of effluent and contains a high strength of organic and inorganic pollutants load. Different types of chemicals like sodium hydroxide, sodium carbonate, and chlorine compounds have been used during the paper-making process. These chemicals are highly responsible for high amounts of biological oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solids (TDS), and total suspended solids (TSS), etc. Floating treatment wetlands (FTWs) technology proven as cost-efficient and aesthetically pleasant technology to treat different types of industrial effluents. The current study deals with the remediation of paper mill effluent by the combined used of macrophytes and bacterial consortium. Two bacterial strains SZ1 and LGW-6 inoculated as consortium to Typha domingensis (southren cattail) in FTWs to evaluate their capacity to detoxify the paper mill effluent. In green house experiment, the reduction in the BOD (87%), COD (93%), and TDS (94%) were observed in T2 where T. domingensis and bacterial consortium were applied in FTWs. Moreover, .highest biomass production, root and shoot length was observed in T2. We concluded that FTWs is the effective and reliable approach for the remediation paper mill effluen
Binning and annotation of saline soil metagenome
(UMT, Lhr, 2023) Zain Abbas
There are about 10 million to 14 million estimated number of earth’s current species. Of them, reporting of 1.2 million has been done and 86% of them have not yet been described. To establish a tree of life and to get a comprehensive idea of all types of species existing on this planet and their phylogenetic relation, genome sequencing of all forms of life has to be done. Extreme environments are fascinating regions on Earth where organisms have adapted to survive and thrive under extreme conditions that are generally inhospitable to most life forms. It is estimate that 1 gram of soil contains billions of microbial species and reporting of only 1-2% will have been done. Modern NGS technologies with their exploitation in microbial field has discovered enormous number of species. The term metagenomics discovered to study the diversity of microbes present in different habitat. In this study, hypersaline soil samples were collected from the Khewra region. The samples were pooled together and total DNA was extracted using MO BIO's PowerSoil DNA Isolation Kit. The sample was sequenced from University of Minnesota, Genomics Center using PacBio SMRT sequencing technology. The reads obtained were further processed for quality control and trimming. There were 965 contigs found out with 65 percent GC content. The structural and functional annotation was done through IMG JGI database system. The binning and phylogenetic analysis was done through Busybee Web for comprehensive and differential composition-based metagenomic binning. It was found out that there were 186 RNA genes and 19909 protein coding genes. Functional annotation showed a fraction of protein coding genes that have function in inorganic ions transport and metabolism, cell wall/envelope biogenesis making the microbes able to survive in extreme saline conditions. The distribution of halophiles such as Haloterrigena, Halorubrum, Streptomyces, Paraoceanicella, Mesorhizobium, and Natronomonas across the saline habitat suggesting their important role in this environment. Further pathway analysis output showed involvement of genes in different pathways such as energy metabolism, amino acid metabolism, xenobiotics degradation, motility. We successfully characterized the saline soil microbial community of khewra mines using PacBio SMRT sequencing technology.
Biochemical characterization of naringenin producing yeast (saccharomyces cerevisiae) strain
(UMT, Lhr, 2023) WAJEEHA UROOJ
Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be exploited for a wide variety of medicinal purposes. These phytochemicals, which are pharmacologically important for clinical use, primarily consist of polyphenols, followed by terpenoids and alkaloids. Numerous published reports indicate the primary role of phytochemicals proven to possess therapeutic potential against several diseases. However, not all phytochemicals possess significant medicinal properties, and only some of them exhibit viable biological effects. Naringenin, a flavanone found in citrus fruits, is known to improve immunity, repair DNA damage, and scavenge free radicals. Despite the very low bioavailability of naringenin, it is known to exhibit various promising biological properties of medicinal importance, including anti-inflammatory and antioxidant activities. It focuses on various aspects related to naringenin, particularly its physicochemical properties. Furthermore, various pharmacological activites of naringenin, such as anticancer, antidiabetic, hepatoprotective, neuroprotective, cardioprotective, nephroprotective and gastroprotective effects, have been discussed along with their mechanisms of action. In our research, yeast was engineered with naringenin pathway genes (TAL, 4CL, CHS, CHI). The production of desired product increased by using different biochemical parameters. I explored various permutations of essential parameters such as pH, temperature, inoculum size, carbon source, nitrogen source, and substrate concentration using Response Surface Methodology (RSM) software. Naringenin compound was extracted from the fermented broth by using ethyl acetate. The extracted compounds was first analyzed by using highthroughput chemicals (sodium Hydroxide, folin, potassium hydroxide, magnesium sulfate, lead oxide and ammonium hydroxide) and subsequently, conducted confirmation test using HPLC. This comprehensive analysis sought to determine the concentration at which our yeast exhibited the highest production of the desired flavonoid, Naringenin. The engineered strain produced naringenin compound which was further optimized with different biochemical parameters. The engineered strain produce maximum compounds when use inoculum size 4%, carbon source 8%, nitrogen 3%, pH 6, temperature 30 oC and subtrate concentration 0.30%. These conditions were confirmed by chemical methods. Among all chemical sodium hydroxide oxide maximally bind with the naringenin compounds and give bright yellow colour. Other methods which need to be add to increase the desired compounds by adding malonyl-CoA and overexpression of pathway genes. As one molecule of naringenin requires three molecules of malonyl-CoA, and malonyl-CoA availability represents a bottleneck in the biosynthesis pathway. The recombinant yeast strain was fed with phenylpropanoid acids and produced naringenin. In conclusion, the production of naringenin using microbial cell factories, including yeast strains such as Saccharomyces cerevisiae, has shown promise. However, yields remain low, and further optimization is needed to increase production. There is no specific study on the biochemical characterization of a naringenin -producing S. cerevisiae strain, studies on naringenin biosynthesis in S. cerevisiae therefore it is the first study to consider biochemical characterization of S. cerevisiae to produce naringenin.
Biochemical characterization of pinocembrin producing yeast (saccharomyces cerevisiae) strain
(UMT, Lhr, 2023) SAULAT NAWAZ SHAH
Flavonoids are a wide-ranging class of naturally occurring compounds with different phenolic structures that can be found in many different places, such as fruits, vegetables, cereals, tea, wine, tree bark, roots, stems, and flowers. Because of their strong antioxidant qualities and ability to reduce inflammation-related symptoms, these substances provide a wide range of health advantages and are simple to include in a diet. The possibilities are bright even though researchers have only begun to explore flavonoids' potential as a medicine. Flavonoids are found throughout the kingdom of plants, where they perform a variety of roles. Pinocembrin is unique among these substances due to its diverse biological properties, which include antiinflammatory, antioxidative, and neuroprotective actions. The synthesis of pinocembrin using microbial cell factories specifically, yeast strains like Saccharomyces cerevisiae has attracted attention recently. We thoroughly investigated primer design, oligonucleotide synthesis, yeast transformation techniques, and yeast genomic DNA extraction in our study. Then, we designed a cassette to facilitate the insertion of plant genes into the S. cerevisiae strain and expedite the manufacture of flavonoids. In order to conduct our study, we genetically altered yeast by adding genes (PAL, 4CL, CHS, CHI) related to the pinocembrin pathway. Through the optimization of several important biochemical parameters, this genetic modification led to an increase in the production of the targeted product. Using Response Surface Methodology (RSM) software, we carefully investigated various combinations of important parameters, such as pH, temperature, inoculum size, carbon supply, nitrogen source, and substrate concentration. Ethyl acetate was utilized to extract pinocembrin from the fermenting broth. A complete study of the extracted substances was carried out, using a range of chemicals (sodium hydroxide, Folin, potassium hydroxide, magnesium sulfate, lead oxide, and ammonium hydroxide). High-Performance Liquid Chromatography (HPLC) was then used to confirm these findings. The goal of this thorough investigation was to ascertain the circumstances in which our yeast strain produced the most pinocembrin, the desired flavonoid. Under particular conditions, our engineered yeast strain showed optimum synthesis of pinocembrin 4% inoculum size, 8% carbon source, 3% nitrogen source, pH 6, 30 °C temperature, and 0.30% substrate concentration. These parameters were confirmed by means of chemical analysis, where in sodium hydroxide was found to have the highest binding affinity with pinocembrin compounds, resulting in brownish color. In order to maximize the yield of the desired compound, extra steps were taken, including the addition of malonyl-CoA and the overexpression of pathway genes. This was required because each molecule of pinocembrin requires three molecules of malonyl-CoA, and the availability of malonyl-CoA represents a bottleneck in the biosynthesis pathway. Ultimately, the production of pinocembrin using microbial cell factories—specifically yeast strains like Saccharomyces cerevisiae shows great promise; however, the yields are still relatively low and require additional optimization. Our research is the first to address the biochemical characterization of S. cerevisiae for pinocembrin synthesis, as there are notably few publications that focus specifically on this topic.
Biomechanical properties of tetragnatha javana spider silk in fieldconditions
(UMT, Lhr, 2023) SEHAR SALEEM
This study delves into the biomechanical properties of Tetragnatha javana spider silk under real- world conditions, surpassing controlled lab environments. Investigating its strength, flexibility, and lightweight nature, the research explores dynamic interactions with environmental elements like humidity, temperature, and natural substrates. Expeditions in diverse climates, from rainforests to deserts, assess spider silk versatility. Orb webs from Tetragnatha javana spiders were collected, and advanced methods, including tensile testing and atomic force microscopy, measured silk properties. Environmental stressors like wind, rain, and UV exposure were analyzed for their impact on silk structural soundness. Results highlight the pivotal role of radial silk in preserving web stability, particularly against flying prey impacts or wind-induced vibrations. Spider silk displays consistent biomechanical traits across variousfield circumstances, demonstrating durability and adaptability. Mean elastic modulus and hardness of radial and spiral silk threads were examined, revealing their dynamic mechanical behavior with a positive correlation to frequency. Radial silk exhibited elastic behavior, while spiral silk demonstrated viscous behavior. Humidity significantly influenced both silk threads, with increased relative humidity decreasing their elastic modulus and hardness. Laser vibrometer analysis measured the damping ratio of radial and spiral silk threads, revealing the notable flexibility and damping of spiral silk. This flexibility enables efficient prey capture, dissipating high kinetic energy throughout the web. Understanding silk behavior in varying frequency and humidity conditions provides insights for creating biomimetic materials tailored for specific applications. The study's findings suggest promising applications of spider silk in biomimetic materials for industries like textiles, medicine, and construction, capitalizing on its unique combination of flexibility and toughness. Keywords: Orb web, Tetragnatha javana, tensile strength, Extensibility, toughness and other Biomechanical properties, Radial and spiral silk thread.
comparative analysis of biochemical analytes in diabetic patients
(UMT, Lhr, 2023) MARYAM ASLAM
Diabetes is a prevalent endocrine disorder that significantly influences 30-40% population in worldwide. In all over the Pakistan, 26% of adult’s population affected by diabetics. According to statistical study, the provinces of Pakistan such as Punjab 21%, Sindh 17%, Baluchistan 20% and in KPK 17% population affected by Diabetics. The study reported that 33% of population of Lahore which is undiagnosed affected by diabetics. This study was conducted to evaluate the effect of diabetics on Liver Function Test, Renal Function Test, HbA1c and Complete blood count. The biochemical and hematological parameters of diabetes patients were performed and data was analyzed by using SPSS Software. The research involved 568 patients in total, with 318 (56%) are male and 250 (44%) are female. We classified the patient’s data into three categories’ according to their HbA1c level. first is normal patients 28% which range of HbA1c 4.0% to 5.7%, second is pre-diabetics (23.4 %) and range is 5.8% to 6.4% and third one is diabetics (48.6 %) and HbA1c > 6.5%. The results Diabetic patients experience hyperglycemia due to elevated Blood glucose levels, affect liver function test, renal function test and CBC result are highly significant and shows positive relation with diabetics. The study findings indicate that a higher proportion of female patients had abnormal liver function test results than male patients.
Comparative analysis of factors associated with initiation and progression of CVST
(UMT, Lhr, 2023) Aun Raza
Cerebral venous sinus thrombosis is a posterior and cavities condition that forms due to the formation of clots in the veins of the bloodstream, specifically in the area of the paranasal sinuses. It can be diagnosed in several ways, including a physical examination and medical history. Various symptoms such as headaches, seizures, vision disturbances, etc. They appear when the effects of caffeine are related to an inadequate metabolism and the cause of this disease increases due to the constriction of the veins that facilitate the increase in blood pressure and the faster formation of clots in them. areas. In this research, different computational methods were used to identify structural and functional changes associated with a change in the wild-type sequence. 38 of 176 nsSNPs in the human CYP1A2 gene were predicted by a combination of computational methods. As functional variables. To look for possible connections with pathogenicity, functional nsSNPs were further examined. The result was that 18 nsSNPs were predicted as pathogenic, among which variants G73R, G73W, R108Q, R108W, E168K, E346K, R431W, F432S, and R456H were also found to be associated with pathogenicity. These results provide new insights into the structure-function association in CYP1A2, CVST and other CYPs and can be taken into account when planning experimental investigations. To fully understand the links and causes of diseases, it is necessary to use more sophisticated methods.
Comparison between microarray and rna seq data of rheumatoid arthritis patients from both blood and synovial fluid
(UMT, Lhr, 2023) Laiba Tahir
The joints are largely affected by the chronic inflammatory illness known as rheumatoid arthritis (RA). Asymmetrically attacking the exact same joints on both sides of the body, it is characterized by swelling, stiffness, discomfort, and inflammation in the joints. However, rheumatoid arthritis can also impact the body's various organs and functions. In our study we aimed to identify hub genes that have a role to play in the occurrence of rheumatoid arthritis from microarray and RNA seq data from both blood and synovial fluid. To those means we used a microarray blood sample dataset GSE15573 (18 RA patients and 15 controls), a microarray synovial fluid sample dataset GSE10500 (5 RA patients and 3 controls) and a RNA seq dataset GSE154474 (3 blood neutrophil RA patients and 3 synovial fluid neutrophil RA patients). By taking a bioinformatics approach we were able to identify ten hub genes (HBB, RGMB, AXIN2, LEF1, TCF7, DMTN, HBA1, HBA2, KRT5, NOG). We were able to conclude that the identified hub genes all have potential to act as biomarkers for rheumatoid arthritis.
computational analysis of potential repellents against economically important insects
(UMT, Lhr, 2023) SANA NASIM
Mosquitoes are vectors for multiple diseases caused by bacteria, viruses, and protozoa. Because mosquitoes convey a variety of illnesses, the exponential population growth of mosquitoes poses a serious threat to many countries. Because of the lactic acid found in human sweat, mosquitoes are attracted to humans. A chemical that works locally or remotely to keep insects from biting people or animals' skin is known as an insect repellent. The use of plant-based repellents has gained popularity again recently due to their abundance of bioactive phytochemicals that are safe and biodegradable into byproducts that are not harmful and can be tested for insecticidal and repellent properties. Most plants create a variety of chemicals to stave against attacks by insects that consume plants, or phytophagous insects. In this study, main focus is on domain of computational analysis in the pursuit of potential repellent compounds against economically important mosquito species. Specifically, we delve into the intricate molecular world of mosquitoes and their interaction with twoprominent plant species, Mari Gold (Tagetes spp.) and English Lavender (Lavandula angustifolia). These plants, due to their aromatic properties, hint at the presence of chemical constituents that may possess the ability to repel mosquitoes and provide a novel avenue for pest management. This study is designed to: investigate the interactions between mosquito proteins and specific compounds present in the plant repellents, i.e., Mari Gold and English Lavender. Various bioinformatics tools including PDB, Dr. Duke, modeler 10.1, chimera 1.15, PubChem, Server NCBI, and MOE are used in the research. The docking process showed the interactions between proteins of mosquitoes and the phytochemicals. DFT confirmed the energy gapsand verified the results. After screening selecting phytochemicals, the lowest energy gap is of antheraxanthin which is 0.08144 kcal/mol. So this phytochemical has high reactivity with protein and low binding energy gap So, Antheraxanthin proved to be the best phytochemical to repel insects.
Computational analysis predicting deleterious variants in fbxo31 gene
(UMT, Lhr, 2023) Amina Khawar
Intellectual developmental disorder is an autosomal recessive disorder characterized by severely below overall intellectual functioning together with abnormalities in adaptive behavior. It is often associated with depression, autism, hyperactivity disorder, and attention deficit. It is mainly caused due to mutations in the FBXO31 gene. The FBXO31 gene is located on chromosome 16 contains nine exons and encodes for 539 amino acid proteins and works as a centrosomal E3 ubiquitin ligase together with SKP1 and Cullin-1. The complex of FBXO31, SKP1 and Cullin-1 is significant for axonal identity and neuronal morphogenesis. Mutations in the FBXO31 gene lead to the deregulation of this complex and its subunits resulting in intellectual disability. In this study, bioinformatic approach has been used to predict the highly pathogenic missense and splice site variants of the FBXO31 gene that caused the deregulation of Skp/Cullin/F-box (SCF) ubiquitin E3 ligase complex. For the screening of pathogenic variants of FBXO31 gene multiple analysis such as missense, stability, post translational modification, conservation, and splice site analysis was done. The pathogenic variants were retrieved from gnomAD and analyzed by missense and splice site variation analysis. For missense analysis, CADD, CAPICE and metaSNP tools were used. Pathogenicity and stability of the variants analyzed by web tools predicted 89 highly pathogenic missense variants and among these 89 variants, 8 were highly destabilizing on the basis of Gibbs Free energy predicted by Duet and DynaMut. The functional analysis of deleterious variants done by Mutpred tool and it was predicted that 85 pathogenic variants disturbing the function of the protein. Moreover, UCSF chimera utilized to check the clashes and 21 deleterious variants clashing with their surrounding residues in the structure of protein. Furthermore, Consurf tool utilized to check the impact of the pathogenic variants on the conserved regions of the protein and 42% gene predicted as conserved. PTM analysis done by utilizing Scan Prosite and NetSurf2.0 and it was predicted that 4/89 pathogenic variants are disturbing the post translational modification sites of FBXO31 gene. Moreover, splice sites analysis was also done by SPiCE v2.1, Splice AI and Mutation Taster and 6 pathogenic variants predicted to affect the splicing mechanism of the FBXO31 gene. This study proved that these variations have a significant role in the deregulation of FBXO31 complex that leads to intellectual disability. FBXO31 deleterious variants predicted in this study can be further analyzed on cell assays.
Heavy Metal Resistant Purple Non-Sulfur Bacteria Isolated from Local Pond in Lahore
(UMT, Lhr, 2023) Mahnoor
Purple non sulfur bacteria are phototrophic bacteria belonging to the group Proteobacteria. PNSB give reddish brown to purple color when grown in anaerobic conditions and incandescent light. PNSB are known to possess diverse metabolic activities and hence are of great biotechnological interest. Heavy metals such as arsenic, mercury, cadmium, chromium and nickel are toxic for the environment and can cause many health-related problems. PNSB can help in the detoxification of heavy metals from the environment. In this study, PNSB were isolated from different ponds located in Model town park and from a pond located near Kot Lakhpat jail in Quaid-e-Azam industrial state, Lahore. PNSB were screened for resistance against different toxic metals. The process of characterizing and identifying PNSB combined morphological, biochemical, physiological, and molecular methods. These PNSB isolates were gram negative. To better define PNSB, several physiological tests can be carried out. When PNSB growth was investigated at various pH values and temperatures, all isolates were able to grow at 25 to 40℃, however, maximum growth occurred at 30 and 37℃. PNSB generate pigments including bacteriochlorophylls and carotenoids, which gives them their purple shade. The pigmentation of all PNSB isolates was reddish brown to purple shade. The hydrogen gas generated by PNSB photosynthesis is a clean and renewable energy. For every PNSB isolate, the gas generation experiment was carried out. With the exception of MNP2, MNP4, and MNP7, all outcomes were positive. PNSB were analyzed for resistance against different concentrations of arsenic, cadmium, mercury, chromium and nickel. The maximum concentration of arsenate, arsenite, chromium, cadmium, mercury and nickel resisted by PNSB were 40mM for arsenate, 10mM for arsenite, 5mM for chromium, 2.5mM for cadmium, 2.5 mM for mercury and 5mM for nickel. Growth curve pattern of PNSB was analyzed both in absence and presence of arsenic. The phylogenetic connection of PNSB species is frequently ascertained using 16S rRNA gene sequencing. Genomic DNA was isolated and 16S rRNA gene was amplified using PCR. The amplicons were sequenced from Macrogen, Korea. These PNSB can be utilized to detoxify arsenic along with production of hydrogen.
Identification of deleterious variations causing cognitive impairement
(UMT, Lhr, 2023) Maria Bibi
Intellectual developmental disorder is an autosomal recessive disorder with abnormalities in adaptive behavior. Protein arginine methytransferase 7 involved in the methylation of arginine residue in post translational modification. It catalyzes the transfer of methyl group to the nitrogen of arginine residue from s-adenosyl-l-methionine. This translational modification involves in the several biological processes, e.g. mRNA splicing, signal transduction, protein translocation, DNA repair, and transcriptional control. I reported 5 siblings from normal parents and exome sequencing revealed that 14 years old female has novel non-synonymous, homozygous variant chr16 68337521, NM_001184824; c.304G>A; p.Gly102Arg in exon 5 of PRMT7 gene causing a condition known as SBIDDS (short stature, brachydactyl, intellectual, developmental disability seizers) syndrome. In this study further bioinformatics approach has been used to predict the other pathogenic variants besides the results of bench work. The most damaging variants of PRMT7 gene that can affect the functionality and stability of the protein were predicted. The 32 pathogenic variants of missense and 6 of splice sites were retrieved from gnomad and CADD. Further different databases being used for different analysis over missense variants such as functional analysis, stability analysis, and PTM analysis. Splice site analysis also performed by using several databases. UCSF Chimera was used for interactive visualization. A total of three 3 PTM sites were also predictably disrupted by 32 variants. SPICE and HSF 3.1 were applied to 6 filtered variants to check their disease causing potential. My findings further expand the molecular and clinical spectrum of homozygous PRMT7 mutations that confirmed its association with SBIDDS syndrome. Further bioinformatics approach predicted the correlation of different variants and severity of phenotypes. It is expected that an extensive in silico analysis can determine the likely pathogenic variations for further in vitro experimental analysis.
Identification of hub genes associated with fanconi anemia via integrated bioinformatic analysis
(UMT, Lhr, 2023) Salman Haider
The Genetic disease FA or Fanconi Anemia is a disorder that is very rare and that cause different genetic changes and different chemical and physical abnormalities in children. The prevalence of the disease is 1 out of 1600000 and present in all ethnic groups and populations but the high ratio of prevalence is present in Jewish, Afrikaans and Spanish communities. The disease symptoms have been confused for a long time with aplastic anemia and different other types of cancers due to its effectiveness on the organs, organ system, skeletal bones, hematological effects including low blood number for platelets, white blood cells and red blood cells. The most reliable treatment is bone marrow transplant although research and advancement are being made on gene therapy and drug therapy. The age expectancy despite of research and treatment being in progress is not more than 30 years. The genetic mutation in one of the 22 genes was considered responsible for the cause of disease in early researches. The scientists later on grouped 23 genes called FANC genes which were mainly affected by mutation causing the Fanocni Anemia disorder. My work and research in the BioGRID project show a total 69 genes obtained from the database and after a very careful analysis of the literature, the gene number increased to 71. All the genes were set in a table with their gene symbol, name and characteristics. The PPI (ProteinProtein Interaction) network was made using STRING, visualized using Cytohubba, a plugin of Cytoscape to find out the main responsible top 10 hub genes of Fanconi Anemia. The GO and KEGG pathway analysis were also made using the DAVID bioinformatics. The obtained results of top 10 hub genes and all components of biological, cellcular, pathway nature could help researchers for designing effective drugs in the treatment of Fanconi Anemia and better understanding of the disease genetics.
Impact of lactation stages on somatic cell count and milk components on nilli-ravi and kundi breeds
(UMT, Lhr, 2023) Rehana Shaheen
This study was conducted on two buffalo breeds, Nilli-Ravi and Kundi, and aims to provide valuable insights into the variations of milk components and somatic cell count (SCC) with respect to breed and lactation stages. A total of 30 milk samples from two buffalo breeds (Nilli-Ravi and Kundi) were included and divided into three groups (early, mid, late) based on their stage of lactation. Milk fat % by the Gerber method, protein by Kjeldahal method, on a Neubauer chamber under a light microscope, and other milk components such as ash, solid not fat (S.N.F), Total solids (T.S), acidity, pH were estimated by the official method of AOAC. Data were evaluated on SPSS to know the significant variation by one-way ANOVA and Pearson’s correlation was employed to know the relationship. This study indicates that the Nilli-Ravi breed exhibits significantly(P<0.05) higher fat (6.73%), protein (3.55%),S.N.F (9.54%), SCC (1.35x105 cells/ml), and T.S(9.54%) compared to the Kundi breed with fat (6.48%), protein (3.33%), SCC (1.09x105 cells/ml), S.N.F (9.0%), and Total solids(16.08%). Though, no significant differences were found between the breeds in terms of acidity, ash%, and pH. The present investigation revealed a consistent and synchronized fluctuation pattern in milk fat, protein, S.N.F%, T.S%, and SCC in both the Nilli-Ravi and Kundi breeds. The observed trend exhibited an initial elevation in concentration, followed by a gradual decline during the mid-lactation stage, and reaching a peak at the final stage. In Nilli-Ravi breed significant variation at early, mid, and late stages in fat % (p < 0.004), S.N.F % (p < 0.03), T.S % (p < 0.04) was observed but the non-significant difference was observed in protein (p > 0.11) percentage at each lactation stages. In Kundi breed Significant variation at early, mid, and late stages in fat percentage (p < 0.002), protein (p < 0.007) percentage, and T.S% (p < 0.01), but non-significant differences were observed in S.N.F % (p >0.13) in Kundi breeds. Although no significant differences were found at early, mid, and late stages in ash%, acidity, and pH% based on lactation stage within each breed. In Pearson correlation significant and consistent negative correlation was observed between SCC and milk components, decrease in fat% (r = -0.602, p = 0.001), protein% (r = -0.479, p = 0.007), and S.N.F (r = -0.425, p = 0.019) as SCC increase. In conclusion, understanding the role of SCC , the influence of the lactation stage, and the selection of high-performing breeds Nilli-Ravi as a comparison to Kundi are ensuring the production of high-quality dairy products at an industrial level
In silico analysis of protein inhibitors of trypanosoma evansi
(UMT, Lhr, 2023) INAYAT ULLAH KHAN
Trypanosoma evansi is the first pathogenic mammalian protozoan. It causes Surra disease in animals such as horses, camels and water buffaloes. It has a global selection of hosts. It belongs to the Trpanosomatidae family and there are two types of circular DNA molecule: Maxi circles and mini circles; from derived T. brucei. It is characterized by various symptoms such as weight loss, progressive anemia and weakness; swelling of the lower parts of the body; the lymph node may also be swollen; nervous symptoms such as head tilt, vertigo, blindness, hypersensitivity; miscarriage, infertility and stillbirth; chronic course with high mortality and can last up to 2 years; death can occur within 2 weeks to 2 months. Today, drugs are used to treat infections, but the animal does not fully recover. These drugs are toxic to animals and show resistance. T. evansi is a terrible protozoan for dromedaries and horses. Phytochemicals are extracted from plants to treat various diseases. Active compounds obtained from plant parts such as leaves, roots, seeds or fruits can be used to treat several diseases without harming the host. In this study, the plant families Meliaceae, Moraceae, Moringaceae, Ranunculaceae, Zingiberaceae, Fabaceae, Aceraceae, Apocynaceae, Asteraceae, Polygonaceae and Poaceae show that they all have the highest medicinal properties. The main goal is to block the pathogen's protein that helps it to invade the host. Various bio-informatics tools such as PDB, Dr. Duke, UCSF Chimera 1.16, PUB Chem, NCBI, Discovery Studio Visualizer, Protein Molecular Weight Server, Gaussian View 09. The study uses zinc pharmer, zinc 15. In addition, the potential of phytochemicals to be used as medicines is tested by testing their various properties such as blood-brain barrier (BBB), GI absorption, solubility, Lipinski's rule of 5, toxicity, carcinogenicity and mutagenicity. The docking process revealed the interactions between the proteins and the ligands of the causative agent. DSV is used to visualize the interaction. DFT confirmed the energy gaps and confirmed the results. In comparison, zinc farmer is an online server that has less energy and is used instead of phytochemicals. After screening more than 3000 phytochemicals and selecting 224, LICOISOFLAVANONE and LUTEOLIN-7-GENTIOBIOSIDE are found to be the best phytochemicals to prevent Trypanosoma evansi infection
In silico interaction studies of spike protein from different SARS-COV-2 variants with its angiotensin-converting ENZYME-2 receptor with respect to geographical regions
(UMT, Lhr, 2023) Ayesha Amin
The emergence of SARS-CoV-2 in late 2019 resulted in the global pandemic of Coronavirus disease 2019 (COVID-19), causing significant disruptions in various aspects of society. SARSCoV-2 belongs to the beta Coronavirus family and is highly infectious, primarily spreading through respiratory droplets. Its genome consists of a single-stranded RNA encoding structural and nonstructural proteins. The spike protein plays a crucial role in viral attachment to host cells through interaction with the ACE2 receptor. Other structural proteins include the envelope, nucleocapsid, and membrane proteins. The virus also encodes 16 nonstructural proteins involved in various aspects of its life cycle, serving as potential targets for drug development. Understanding the structural and nonstructural proteins of SARS-CoV-2 is essential for comprehending its lifecycle and developing effective therapeutic strategies. This study provides an overview of the viral proteins, their functions, and the lifecycle of SARS-CoV-2, offering valuable insights for further research and the development of antiviral interventions.
In-silico analysis of coding and non-coding variants in mettl5 gene
(UMT, Lhr, 2023) Muhammad Haris Ali Khan
Its relationship to intellectual impairment (ID) in people with METTL5 gene. Mutations in METTL5 have been linked to mild to severe forms of ID, which can manifest as deformities, seizures, microcephaly, short stature, and muscular hypotonia. The METTL5 gene is present on chromosome no 2. The METTL5 gene form a complex with TRMT112 and work normally. Due to knockdown of TRMT112 molecule the METTL5 gene expression is low in the body. In this study, bioinformatics approach has been used to predicted the coding and noncoding variants that effect the function, stability, splice site and non-coding region of METTL5 gene. A total of 66 missense variants in METTL5 gene were predicted to be pathogenic by CADD and Meta-SNP. These mutations were analyzed by CUPSAT, DynaMut and DUET for their effect on stability and variations were predicted pathogenic overall. 60 of the 61 variations were predicted to be affecting the function of the gene by Mutpred .4 variations p.Asp49Tyr, p.Asp103Gly, p.Leu76Trp and p.Gly130Glu were predicted by ScanProsite and NetSurfP 2.0 to affecting the PTM mechanism of the protein. These 61 missense variants were visualized by UCSF Chimera. There were no clashes found in protein structure after mutation. CADD predicted 15splice site variants, out of 15 variants 10 variants were pathogenic and further analyzed for their effect by SPiCE v2.1, Splice AI and Mutation Taster. None of variations with uncertain significance found in splice site were predicted by Splice AI, 4 out of 9 variants were predicted pathogenic by SPiCE v2.1 and 2 out of 9 variants were predicted deleterious by Mutation Taster to affecting the splicing site of the gene. The Regulome DB 2.2 was used for the analysis of non-coding variants and predicted that less effect on the TF binding site of METTL5 gene. The protein plus ligand analysis showed that 2 out of 5 mutated residues show no interaction with the ligand and 3 out of 5 mutated residues show the interaction with ligand structure. Data can be used for the early detection of mutations in METTL5 by cloning the mutation individually and determining their effect in vectors by mutagenesis. These findings contribute to our understanding of METTL5 gene representing complex disease features. This study demonstrated the importance of bioinformatics in determining highly pathogenic variants associated with the functional and structural relationship of METTL5
In-silico analysis to identify pathogenicity of mutations in CBS gene
(UMT, Lhr, 2023) Maliha Noor
Homocystinuria is an autosomal recessive disease related with neurological and physical abnormalities. It is associated with facial deformities, skeletal deformation, ocular disorders, cardiac problems and intellectual disability. Homocystinuria is mainly caused due to mutations in CBS gene which encodes Cystathionine betasynthase enzyme which, catalyzes methionine into homocysteine. In-silico approach was used to predict the pathogenicity associated with CBS gene known to be involved in Homocystinuria. The study’s goal was to emphasize the importance of CBS gene as well as to uncover pathogenic variants related to CBS gene for aiding in the diagnosis and treatment of homocystinurai. The variants were retrieved from gnomAD and analyzed by multiple bioinformatics tools and databases i.e., missense variation analysis, Stability, function, conservation and PTM mechanism analysis and also for splice site affecting variations were also analyzed. A total of 54 missense variants in CBS gene were predicted to be pathogenic by CADD and meta-SNP. These mutations were analyzed by Cupsat, Dynamut and Duet for their effect on stability and 9 of 54 variations were predicted pathogenic overall. 51 of the 54 variations were predicted to be effecting the function of the gene by Mutpred and 42% of the gene structure was predicted to be conserved by Consurf. 3 variations G134E, G134R and G388N were predicted by Scan prosite and netsurf to effecting the PTM mechanism of the protein. These 54 missense variants were visualized by Chimera. CADD predicted 751 splice site variants out or which 20 were pathogenic and further analyzed for their effect by SPiCE v2.1, Splice AI and Mutation Taster. None of variations with uncertain significance found in splice site were predicted to effecting the splicing mechanism of the gene. data can be used for he early detection of mutations in Cystathionine beta-synthase enzyme by cloning the mutation individually and determining their effect in vectors by mutagenesis.These findings contribute to our understanding of CBS gene representing complex disease features. This study demonstrated the importance of bioinformatics in determining highly pathogenic variants associated with the functional and structural relationship of Cystathionine beta-synthase protein.

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