Biology subjects

Hamdan, F.

Publications and source records attributed to Hamdan, F..

7 recordsLinked to original sources

bioRxiv2025

Valuing conservation and natural wealth: The blue economy of manta ray watching in the Maldives

Amid declining manta ray populations globally, the well-established and growing manta ray tourism industries generate substantial economic benefits and aid protective legislation for these threatened elasmobranchs. As flagship species, manta rays are a drawcard for marine wildlife tourism and a gateway for engaging the public and communities in conservation. Healthy marine ecosystems are the key drivers of employment and economic sustainability for island nations such as the Maldives. However, there are many stakeholders competing for these shared resources, which can result in environmental degradation. Economic evaluations are a powerful tool for justifying the conservation efforts of threatened species and natural areas, especially in light of competing stakeholders. Using tour operator surveys (n=106) and data mining, this study provides an updated assessment of manta ray watching tourism in the Maldives, and represents the first national evaluation of its total economic and socio-economic benefits. In 2021, manta ray tourism in the Maldives generated an estimated US$227.3 million, including US$39 million on manta ray focused diving and snorkelling excursions, and US$188.3 million in related tourist expenditure. This represented 4.8% of the national Gross Domestic Product. This industry appears to have grown around 380% since 2008 (US$8.1 million) and manta ray watching is now offered by 80% of tourism operators nation-wide. Our findings revealed that manta rays hold intrinsic value and cultural significance within local communities. Acknowledging this, the flow-on benefits to the community extend beyond this industry, reaching local businesses, employed staff, and the government with the total economic benefits of the manta ray tourism industry were estimated at over US$311 million per year. Such value highlights the significance of manta rays for this nation and the need for effective management centred on manta ray conservation to safeguard future prosperity and mitigate the potential impact of tourism on manta ray populations.

ecology↗

bioRxiv2025

CertPrime: a new oligonucleotide design tool for gene synthesis

The design of oligonucleotides with uniform hybridisation temperatures is essential for successful gene synthesis. However, current computational tools for oligonucleotide design face significant limitations, including difficulties in processing long DNA sequences, poor adaptability to specific experimen- tal conditions, limited control over oligonucleotide length, and challenges in minimising spurious dimer formation. To address these issues, we devel- oped CertPrime, an innovative tool designed for scalable and efficient han- dling of long DNA sequences. CertPrime enables precise customisation of experimental parameters, provides flexibility to limit the maximum oligonu- cleotide length, and generates designs with reduced deviations in melting temperatures across overlapping regions compared to existing tools. We experimentally compared CertPrime designs with benchmark design meth- ods for a complex DNA sequence and found that CertPrime design led to more efficient gene assembly, significantly reducing the occurrence of non- specific bands. These results make CertPrime a powerful and versatile tool for oligonucleotide design in gene synthesis applications. HighlightsO_LICertPrime improves oligonucleotide design by minimising melting-temperature deviations and spurious dimer formation. C_LIO_LIThe new tool enhances gene-synthesis efficiency, allowing a precise con- trol over oligonucleotide lengths and experimental parameters. C_LIO_LICertprime is a scalable tool capable of designing over 99% of the human genome with optimized sequence assembly C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/650686v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@2032aaorg.highwire.dtl.DTLVardef@1de509borg.highwire.dtl.DTLVardef@7e2148org.highwire.dtl.DTLVardef@bb3dd2_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2021

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Beside the isolation and identification of MHC-I restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective anti-tumor CD8+ T cell mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific anti-tumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate >8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and the HEX software. The latter is a tool previously developed by Chiaro et al. (1), able to identify tumor antigens similar to pathogen antigens, in order to exploit molecular mimicry and tumor pathogen cross-reactive T-cells in cancer vaccine development. The generated list of candidates (twenty-six in total) was further tested in a functional characterization assay using interferon-{gamma} ELISpot (Enzyme-Linked Immunospot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, non-treated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach.

cancer biology↗

bioRxiv2021

A personalized anti-cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella

Common vaccines for infectious diseases have been repurposed as cancer immunotherapies. Intratumoural administration of these repurposed vaccines can induce immune cell infiltration into the treated tumour. Here, we have used an approved trivalent live attenuated measles, mumps, and rubella (MMR) vaccine in our previously developed PeptiENV anti-cancer vaccine platform. Intratumoural administration of this novel MMR-containing PeptiENV anti-cancer vaccine significantly increased both intratumoural as well as systemic tumour-specific T cell responses. In addition, PeptiENV therapy, in combination with immune checkpoint inhibitor therapy, significantly improved tumour growth control and survival as well as increased the number of mice responsive to immune checkpoint inhibitor therapy.

immunology↗

bioRxiv2021

Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin

Intratumoural bacillus Calmette-Guerin (BCG) therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumour. Here, we have developed a novel cancer vaccine platform based on BCG that can direct BCG-induced immune responses against tumour antigens. By physically attaching tumour-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoural T cell-specific immune responses towards the attached tumour antigens. These therapeutic peptides can be attached to the mycobacterial outer membrane using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat, N-terminally fused to the tumour-specific peptides. Alternatively, therapeutic peptides can be conjugated with a poly-lysine sequence N-terminally fused to the tumour-specific peptides. Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the anti-tumour responses of BCG can be significantly improved by coating the BCG with tumour-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-PD-1 immune checkpoint inhibitor therapy, the number of responders to anti-PD-1 immunotherapy can be significantly increased.

cancer biology↗

bioRxiv2019

Systematic re-annotation of 191 genes associated with early-onset epilepsy unmasks de novo variants linked to Dravet syndrome in novel SCN1A exons

The early infantile epileptic encephalopathies (EIEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 novel putative transcript models. The extended transcriptional footprint of these genes allowed for 294 intronic or intergenic variants, found in human mutation databases, to be reclassified as exonic, while a further 70 intronic variants were reclassified as splice-site proximal. Using SCN1A as a case study due to its close phenotype/genotype correlation with Dravet syndrome, we screened 122 people with Dravet syndrome, or a similar phenotype, with a panel of novel exon sequences representing eight established genes and identified two de novo SCN1A variants that now, through improved gene annotation can be ascribed to residing among novel exons. These two (from 122 screened patients, 1.6%) new molecular diagnoses carry significant clinical implications. Furthermore, we identified a previously-classified SCN1A intronic Dravet-associated variant that now lies within a deeply conserved novel exon. Our findings illustrate the potential gains of thorough gene annotation in improving diagnostic yields for genetic disorders. We would expect to find new molecular diagnoses in our 191 genes that were originally suspected by clinicians for patients, with a negative diagnosis.

genomics↗

bioRxiv2017

Genome-wide characterization of copy number variants in epilepsy patients

Epilepsy will affect nearly 3% of people at some point during their lifetime. Previous copy number variants (CNVs) studies of epilepsy have used array-based technology and were restricted to the detection of large or exonic events. In contrast, whole-genome sequencing (WGS) has the potential to more comprehensively profile CNVs but existing analytic methods suffer from limited accuracy. We show that this is in part due to the non-uniformity of read coverage, even after intra-sample normalization. To improve on this, we developed PopSV, an algorithm that uses multiple samples to control for technical variation and enables the robust detection of CNVs. Using WGS and PopSV, we performed a comprehensive characterization of CNVs in 198 individuals affected with epilepsy and 301 controls. For both large and small variants, we found an enrichment of rare exonic events in epilepsy patients, especially in genes with predicted loss-of-function intolerance. Notably, this genome-wide survey also revealed an enrichment of rare non-coding CNVs near previously known epilepsy genes. This enrichment was strongest for non-coding CNVs located within 100 Kbp of an epilepsy gene and in regions associated with changes in the gene expression, such as expression QTLs or DNase I hypersensitive sites. Finally, we report on 21 potentially damaging events that could be associated with known or new candidate epilepsy genes. Our results suggest that comprehensive sequence-based profiling of CNVs could help explain a larger fraction of epilepsy cases.\n\nAuthor summaryEpilepsy is a common neurological disorder affecting around 3% of the population. In some cases, epilepsy is caused by brain trauma or other brain anomalies but there are often no clear causes. Genetic factors have been associated with epilepsy in the past such as rare genetic variations found by linkage studies as well as common genetic variations found by genome-wide association studies and large copy-number variants. We sequenced the genome of[~] 200 epilepsy patients and[~] 300 healthy controls and compared the distribution of deletion (loss of a copy) and duplication (additional copy) of genomic regions. Thanks to the sequencing technology and a new method that takes advantage of the large sample size, we could compare the distribution of small copy- number variants between epilepsy patients and controls. Overall, we found that small variants are also associated with epilepsy. Indeed, the genome of epilepsy patients had more exonic copy- number variants, especially when rare or affecting genes with predicted loss-of-function intolerance. Focusing on regions around genes that have been previously associated with epilepsy, we also found more non-coding variants in epilepsy patients, especially deletions or variants in regulatory regions. Finally, we provide a list of 21 regions in which we found likely pathogenic variants.

genomics↗