Characterizing domain-specific open educational resources by linking ISCB Communities of Special Interest to Wikipedia.

MOTIVATION: Wikipedia is one of the most important channels for the public communication of science and is frequently accessed as an educational resource in computational biology. Joint efforts between the International Society for Computational Biology (ISCB) and the Computational Biology taskforce of WikiProject Molecular Biology (a group of expert Wikipedia editors) have considerably improved computational biology representation on Wikipedia in recent years. However, there is still an urgent need for further improvement in quality, especially when compared to related scientific fields such as genetics and medicine. Facilitating involvement of members from ISCB Communities of Special Interest (COSIs) would improve a vital open education resource in computational biology, additionally allowing COSIs to provide a quality educational resource highly specific to their subfield. RESULTS: We generate a list of around 1500 English Wikipedia articles relating to computational biology and describe the development of a binary COSI-Article matrix, linking COSIs to relevant articles and thereby defining domain-specific open educational resources. Our analysis of the COSI-Article matrix data provides a quantitative assessment of computational biology representation on Wikipedia against other fields and at a COSI-specific level. Furthermore, we conducted similarity analysis and subsequent clustering of COSI-Article data to provide insight into potential relationships between COSIs. Finally, based on our analysis, we suggest courses of action to improve the quality of computational biology representation on Wikipedia.

Adapting beyond borders: Insights from the 19th Student Council Symposium (SCS2023), the first hybrid ISCB Student Council global event.

Summary: The 19th ISCB Student Council Symposium (SCS2023) organized by ISCB-SC adopted a hybrid format for the first time, allowing participants to engage in-person in Lyon, France, and virtually via an interactive online platform. The symposium prioritized inclusivity, featuring on-site sessions, poster presentations, and social activities for in-person attendees, while virtual participants accessed live sessions, interactive Q&A, and a virtual exhibit hall. Attendee statistics revealed a global reach, with Europe as the major contributor. SCS2023's success in bridging in-person and virtual experiences sets a precedent for future events in Computational Biology and Bioinformatics. Availability and Implementation: The details of the symposium, speaker information, schedules, and accepted abstracts, are available in the program booklet (https://doi.org/10.5281/zenodo.8173977). For organizers interested in adopting a similar hybrid model, it would be beneficial to have access to details regarding the online platform used, the types of sessions offered, and the challenges faced. Future iterations of SCS can address these aspects to further enhance accessibility and inclusivity.

1st ASCS: Expanding the ISCB Student Council Symposia to Asia.

Since 2004, the ISCB Student Council (ISCB-SC) has successfully organized Student Council Symposia across several continents, including North America, Latin America, Europe, and Africa, as well as local events led by more than 25 Regional Student Groups (RSG) across the world. The ISCB-SC Symposia provide students and early career researchers the chance to showcase their work at an international venue in a format that includes keynote talks, round table discussions, workshops, and more. After several efforts spanning several years to build enough critical mass in the region, we have successfully organized the first Asian Student Council Symposium (1st ASCS). This article discusses the organizational details of this unprecedented event, the challenges faced, and the lessons learned.

Computational design of medicinal compounds to inhibit RBD-hACE2 interaction in the Omicron variant: unveiling a vulnerable target site.

The COVID-19 pandemic, caused by SARS-CoV-2, has globally affected both human health and economy. Several variants with a high potential for reinfection and the ability to evade immunity were detected shortly after the initial reported case of COVID-19. A total of 30 mutations in the spike protein (S) have been reported in the SARS-CoV-2 (BA.2) variant in India and South Africa, while half of these mutations are in the receptor-binding domain and have spread rapidly throughout the world. Drug repurposing offers potential advantages over the discovery of novel drugs, and one is that it can be delivered quickly without lengthy assessments and time-consuming clinical trials. In this study, computational drug design, such as pharmacophore-based virtual screening and MD simulation has been concentrated, in order to find a novel small molecular inhibitor that prevents hACE2 from binding to the receptor binding domain (RBD). three medicinal compound databases: North-East African, North African, and East African were screened and carried out a multi-step screening approach that identified three compounds, which are thymoquinol 2-O-beta-glucopyranoside (C1), lanneaflavonol (C2), and naringenin-4'-methoxy-7-O-Alpha-L-rhamnoside (C3), with excellent anti-viral properties against the RBD of the omicron variant. Furthermore, PAIN assay interference, computation bioactivity prediction, binding free energy, and dissociation constant were used to validate the top hits, which indicated good antiviral activity. The three compounds that were found may be useful against COVID-19, though more research is required. These findings could aid the development of novel therapeutic drugs against the emerging Omicron variant of SARS-CoV-2.

In silico exploration of Serratia sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin.

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. "Prodigiosin NRPS", among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 µg/mL and 7.81 to 31.25 µg/mL respectively. At concentration 500 µg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 µg/mL pigment where 125 µg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

M gene targeted qRT-PCR approach for SARS-CoV-2 virus detection.

Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is the gold standard method for SARS-CoV-2 detection, and several qRT-PCR kits have been established targeting different genes of the virus. Due to the high mutation rate of these genes, false negative results arise thus complicating the interpretation of the diagnosis and increasing the need of alternative targets. In this study, an alternative approach for the detection of SARS-CoV-2 viral RNA targeting the membrane (M) gene of the virus using qRT-PCR was described. Performance evaluation of this newly developed in-house assay against commercial qRT-PCR kits was done using clinical oropharyngeal specimens of COVID-19 positive patients. The limit of detection was determined using successive dilutions of known copies of SARS-CoV-2 pseudovirus. The M gene based assay was able to detect a minimum of 100 copies of virus/mL indicating its capacity to detect low viral load. The assay showed comparable accuracy, sensitivity and specificity with commercially available kits while detecting all the variants efficiently. The study concluded that the in-house M gene based assay might be an effective alternative for the currently available commercial qRT-PCR kits.

Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

Management of Hemoglobin Disorders During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has become a global public health concern after being first reported in China and has subsequently spread worldwide. It causes mild to severe respiratory illness with some flu-like symptoms. The causal virus behind this disease, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), conceivably attacks the receptors of the respiratory system of the human body but has no strict evidence of attacking the blood cells yet. However, patients with hemoglobin disorders (e.g., sickle cell anemia, thalassemia) are vulnerable to this global health situation due to their clinical complications. Such patients are generally more prone to viral and bacterial infections, which can worsen their physical condition. Some of these patients present immunocompromised conditions, e.g., splenectomized or post-transplant patients. Therefore, they should follow some preventive steps such as shielding as well as the general guidelines for the COVID-19 pandemic. Transfusion dependent patients require regular monitoring for iron overload, and iron chelation therapy may be stopped by the physician depending on the situation. This article reviews the management strategies and provides some crucial recommendations for people in the corner with hemoglobin disorders.

MATE2 Expression Is Associated with Cancer Cell Response to Metformin.

BACKGROUND: There is great interest in repurposing the commonly prescribed anti-diabetic drug metformin for cancer therapy. Intracellular uptake and retention of metformin is affected by the expression of organic cation transporters (OCT) 1-3 and by multidrug and toxic compound extrusion (MATE) 1-2. Inside cells, metformin inhibits mitochondrial function, which leads to reduced oxygen consumption and inhibition of proliferation. Reduced oxygen consumption can lead to improved tumor oxygenation and radiation response. PURPOSE: Here we sought to determine if there is an association between the effects of metformin on inhibiting oxygen consumption, proliferation and expression of OCTs and MATEs in a panel of 19 cancer cell lines. RESULTS: There was relatively large variability in the anti-proliferative response of different cell lines to metformin, with a subset of cell lines being very resistant. In contrast, all cell lines demonstrated sensitivity to the inhibition of oxygen consumption by metformin, with relatively small variation. The expression of OCT1 correlated with expression of both OCT2 and OCT3. OCT1 and OCT2 were relatively uniformly expressed, whereas expression of OCT3, MATE1 and MATE2 showed substantial variation across lines. There were statistically significant associations between resistance to inhibition of proliferation and MATE2 expression, as well as between sensitivity to inhibition of oxygen consumption and OCT3 expression. One cell line (LNCaP) with high OCT3 and low MATE2 expression in concert, had substantially higher intracellular metformin concentration than other cell lines, and was exquisitely sensitive to both anti-proliferative and anti-respiratory effects. In all other cell lines, the concentration of metformin required to inhibit oxygen consumption acutely in vitro was substantially higher than that achieved in the plasma of diabetic patients. However, administering anti-diabetic doses of metformin to tumor-bearing mice resulted in intratumoral accumulation of metformin and reduced hypoxic tumor fractions. CONCLUSIONS: All cancer cells are susceptible to inhibition of oxygen consumption by metformin, which results in reduced hypoxic tumor fractions beneficial for the response to radiotherapy. High MATE2 expression may result in resistance to the anti-proliferative effect of metformin and should be considered as a negative predictive biomarker in clinical trials.

Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin.

BACKGROUND AND PURPOSE: Metformin is commonly prescribed to treat type 2 diabetes, and has additional potential as a cancer prophylactic and therapeutic. Metformin activates AMPK that in turn can launch a p53-dependent metabolic checkpoint. Possible interactions between metformin and radiation are poorly understood. Since radiation-induced signaling also involves AMPK and p53, we investigated their importance in mediating responses to metformin and radiation. MATERIALS AND METHODS: A549 cells, HCT116 cells wildtype or knockout for p53 or MEFs wildtype or double knockout for AMPKα1 and α2 were irradiated in the presence or absence of metformin. The impact of metformin on oxygen consumption and proliferation rates was determined, as well as clonogenic radiation survival. RESULTS: Metformin resulted in moderate radiation protection in all cell lines, irrespective of AMPK and p53. Loss of AMPK sensitized cells to the anti-proliferative effects of metformin, while loss of p53 promoted both the growth inhibitory and toxic effects of metformin. Consequently, overall cell death after radiation was similar with and without metformin irrespective of AMPK or p53 genotype. CONCLUSIONS: The anti-proliferative activity of metformin may confer benefit in combination with radiotherapy, and this benefit is intensified upon loss of AMPK or p53 signaling.