Biology subjects

Syed, K.

Publications and source records attributed to Syed, K..

5 recordsLinked to original sources

bioRxiv2026

Identification and classification of all Cytochrome P450 deposits in the Protein Data Bank

Cytochrome P450 monooxygenases (CYPs/P450s) form a highly diverse enzyme superfamily central to biotechnology, pharmacology, and environmental science. Despite the large number of available structures, identifying and comparing P450 entries in structural repositories remains challenging due to their extreme sequence divergence and inconsistent annotation practices. In particular, many deposits lack the standardized nomenclature (CYPid) and rather rely on legacy or author-defined common names (like P450cam, P450BM-3 and P450-PCN1), which are often inconsistent in formatting and specificity. This is particularly difficult for a superfamily as sequentially diverse as P450s. This hinders reliable retrieval and cross-referencing, making even identification all P450 structures in the database nontrivial. To overcome these obstacles, we developed a structure-guided discovery and validation workflow combining keyword search, Hidden Markov Models, and structural alignment, enabling robust detection and annotation. This strategy identified 1,513 deposits representing 674 unique sequences. All sequences were reannotated using the P450Atlas server and manually verified, confirming high assignment accuracy. In the process, we have also identified five new CYP subfamilies. The resulting dataset constitutes the first rigorously curated, structure-linked registry of P450 enzymes, integrated into a publicly accessible resource and supported by an automated pipeline that periodically scans newly released entries. By unifying structurally validated identification with standardized CYP nomenclature, this work establishes a reliable framework for accurate retrieval, comparison, and future large-scale analyses of P450 enzymes.

bioinformatics↗

bioRxiv2024

Population growth poses a significant threat to forest ecosystems: a case study from the Hindukush-Himalayas of Pakistan

Human population growth and associated increases in anthropogenic activities pose a significant threat to forest ecosystems by diminishing the natural ecosystem services these systems provide. Malam Jabba is located in District Swat Pakistans Hindukush-Himalayan temperate zone, which is renowned for ecotourism and skiing and is rich in timber-producing tree species, medicinal plants, and unique biodiversity; however, the majority of Swat Valleys population relies on Malam Jabba forests for their timber & fuelwood requirements. We examined how the deforestation rate increased with increasing human population density in Pakistans Malam Jabba area of the Hindukush-Himalayas. To identify the forest cover, remote sensing, and geographic information systems were used (RS & GIS). The study areas vegetation was analyzed with the Normalized Divergence Vegetation Index (NDVI) using multitemporal satellite images for the years 1980, 2000, and 2020. The deforestation rate from 1980 to 2020 was then determined using the decay model, and the MATLAB program was used to predict the deforestation rate for the following two decades in relation to the anticipated growth in the human population. Our result revealed that, in the last two decades, the average rate of deforestation increased from 0.7% to 1.93% per year, while the human population of District Swat increased from 1.2 to 2.3 million at a rate of 9% per year. The decay model predicts that the study areas deforestation rate will increase to 2.5% per year over the next two decades due to the forecasted 11.6% per year population growth rate. Human population growth in District Swat, Pakistan has seriously threatened the nearby forest ecosystems, and a future increase in human population will further accelerate anthropogenic activities like unsustanible tourism, fuel and timber wood collection and urbanization. Based on our results, we recommend that: (i) in addition to reforestation programs and sustainable use of forest resources, the government should implement a long-term forest management plan (ii) where the density of forest cover can be sustained at an equilibrium level dependent of population growth pressure (iii) and areas with extreme human pressure should be designated as most important for in situ conservation approach.

ecology↗

bioRxiv2024

Comparison of Alternative pre-mRNA Splicing and Gene Expression Patterns in Midbrain Lineage Cells Carrying Familial Parkinson's Disease Mutations

Parkinsons disease (PD) arises from genetic and environmental factors. Human genetics has identified mutations in [~]20 inherited familial genes linked to monogenic forms of PD. To investigate the effects of individual familial PD mutations, human pluripotent embryonic stem cells (hPSCs) carrying 12 distinct familial PD mutations were differentiated into midbrain lineage cells, including dopaminergic (mDA) neurons. Global gene expression and pre-mRNA splicing patterns were analyzed in midbrain cultures carrying pathogenic PD mutations in the PRKN, SNCA, LRRK2, PINK1, DNAJC6, FBXO7, SYNJ1, DJ1, VPS13C, ATP13A2 and GBA1 genes. We have grouped the analysis of these familial PD mutations to genes expressed in mDA neurons and whose pre-mRNA splicing changes are linked to known PD defects in transport, cytoskeleton, lysosomes and mitochondria. Importantly, we have also shown that subsets of these splicing changes overlap with changes found in PD patient postmortem brains. Mutation-specific pre-mRNA isoforms may function as both diagnostic biomarkers for familial PD-associated genotypes and promising therapeutic targets.

neuroscience↗

bioRxiv2023

IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy

Glioblastoma (GBM) brain tumours lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumours almost always fatally recur. Using RNAseq data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumours, we identified two responder subtypes based on therapy-driven changes in gene expression. In two thirds of patients a specific subset of genes is up-regulated from primary to recurrence (Up responders) and in one third the same genes are down-regulated (Down responders). Characterisation of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms. In Up responders treatment enriches for quiescent proneural GBM stem cells and differentiated neoplastic cells with increased neurotransmitter signalling, whereas Down responders commonly undergo therapy-driven mesenchymal transition. Stratifying GBM tumours by response subtype may lead to more effective treatment. In support of this, modulators of gamma aminobutyric acid (GABA) neurotransmitter signalling differentially sensitise Up and Down responder GBM models to standard treatment in vitro.

cancer biology↗

bioRxiv2017

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of two distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Our analyses discern two biologically distinct variants of anaplastic meningioma with potential prognostic and therapeutic significance.

genomics↗