Genomic surveillance of Rift Valley fever virus: from sequencing to lineage assignment.

Genetic evolution of Rift Valley fever virus (RVFV) in Africa has been shaped mainly by environmental changes such as abnormal rainfall patterns and climate change that has occurred over the last few decades. These gradual environmental changes are believed to have effected gene migration from macro (geographical) to micro (reassortment) levels. Presently, 15 lineages of RVFV have been identified to be circulating within the Sub-Saharan Africa.

Conserved recombination patterns across coronavirus subgenera.

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns.

Increasing African genomic data generation and sharing to resolve rare and undiagnosed diseases in Africa: a call-to-action by the H3Africa rare diseases working group.

The rich and diverse genomics of African populations is significantly underrepresented in reference and in disease-associated databases. This renders interpreting the Next Generation Sequencing (NGS) data and reaching a diagnostic more difficult in Africa and for the African diaspora. It increases chances for false positives with variants being misclassified as pathogenic due to their novelty or rarity.

Expanding the Galaxy's reference data.

Summary: Properly and effectively managing reference datasets is an important task for many bioinformatics analyses. Refgenie is a reference asset management system that allows users to easily organize, retrieve and share such datasets. Here, we describe the integration of refgenie into the Galaxy platform.

The International Virus Bioinformatics Meeting 2022.

The International Virus Bioinformatics Meeting 2022 took place online, on 23-25 March 2022, and has attracted about 380 participants from all over the world. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The participants created a highly interactive scientific environment even without physical face-to-face interactions.

A View on Genomic Medicine Activities in Africa: Implications for Policy.

Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them.

The clinical utility of polygenic risk scores in genomic medicine practices: a systematic review.

Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g.

Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders.

HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). The HIV transactivator of transcription (Tat) protein plays a key role in the neuropathophysiology of HAND. The Tat protein functions by transactivation of viral genes through its interaction with the transactivation response (TAR) RNA element.

Drug repurposing through virtual screening and in vitro validation identifies tigecycline as a novel putative HCV polymerase inhibitor.

The repurposing of marketed drugs for new indications is an elegant strategy to quickly and cost-efficiently address unmet medical needs. The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has been shown to be a valid drug target. We performed structure-based virtual screening to assess the off-label utilization of existing drugs as novel HCV inhibitors.

Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function.

Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred.

High Resolution HLA ∼A, ∼B, ∼C, ∼DRB1, ∼DQA1, and ∼DQB1 Diversity in South African Populations.

Lack of HLA data in southern African populations hampers disease association studies and our understanding of genetic diversity in these populations. We aimed to determine HLA diversity in South African populations using high resolution HLA ∼A, ∼B, ∼C, ∼DRB1, ∼DQA1 and ∼DQB1 data, from 3005 previously typed individuals. We determined allele and haplotype frequencies, deviations from Hardy-Weinberg equilibrium (HWE), linkage disequilibrium (LD) and neutrality test.

Current Status of Next-Generation Sequencing Approaches for Candidate Gene Discovery in Familial Parkinson´s Disease.

Parkinson's disease is a neurodegenerative disorder with a heterogeneous genetic etiology. The advent of next-generation sequencing (NGS) technologies has aided novel gene discovery in several complex diseases, including PD. This Perspective article aimed to explore the use of NGS approaches to identify novel loci in familial PD, and to consider their current relevance.

microRNA profile of Hermetia illucens (black soldier fly) and its implications on mass rearing.

The growing demands on protein producers and the dwindling available resources have made Hermetia illucens (the black soldier fly, BSF) an economically important species. Insights into the genome of this insect will better allow for robust breeding protocols, and more efficient production to be used as a replacement of animal feed protein. The use of microRNA as a method to understand how gene regulation allows insect species to adapt to changes in their environment, has been established in multiple species.

Upregulation of , , and predicts poor prognosis in pediatric acute myeloid leukemia patients with mutation.

Chromosomal translocations and gene mutations are characteristics of the genomic profile of acute myeloid leukemia (AML). We aim to identify a gene signature associated with poor prognosis in AML patients with compared to AML patients with mutations. RNA-sequencing (RNA-Seq) count data were downloaded from the UCSC Xena browser.

Repurposing Based Identification of Novel Inhibitors against MmpS5-MmpL5 Efflux Pump of : A Combined In Silico and In Vitro Study.

In the current era of a pandemic, infections of COVID-19 and Tuberculosis (TB) enhance the detrimental effects of both diseases in suffering individuals. The resistance mechanisms evolving in are limiting the efficiency of current therapeutic measures and pressurizing the stressed medical infrastructures. The bacterial efflux pumps enable the development of resistance against recently approved drugs such as bedaquiline and clofazimine.

Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.

Background: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard.

A framework for the promotion of ethical benefit sharing in health research.

There is an increasing recognition of the importance of including benefit sharing in research programmes in order to ensure equitable and just distribution of the benefits arising from research. Whilst there are global efforts to promote benefit sharing when using non-human biological resources, benefit sharing plans and implementation do not yet feature prominently in research programmes, funding applications or requirements by ethics review boards. Whilst many research stakeholders may agree with the concept of benefit sharing, it can be difficult to operationalise benefit sharing within research programmes.

The COMBAT-TB Workbench: Making Powerful Mycobacterium tuberculosis Bioinformatics Accessible.

Whole-genome sequencing (WGS) is a powerful method for detecting drug resistance, genetic diversity, and transmission dynamics of Mycobacterium tuberculosis. Implementation of WGS in public health microbiology laboratories is impeded by a lack of user-friendly, automated, and semiautomated pipelines. We present the COMBAT-TB Workbench, a modular, easy-to-install application that provides a web-based environment for Mycobacterium tuberculosis bioinformatics.

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred.

The developmentally dynamic microRNA transcriptome of tsetse flies, vectors of animal trypanosomiasis.

Summary: MicroRNAs (miRNAs) are single stranded gene regulators of 18-25 bp in length. They play a crucial role in regulating several biological processes in insects. However, the functions of miRNA in , one of the biological vectors of African animal trypanosomosis in sub-Saharan Africa, remain poorly characterized.

Predicting amplification of using CpG methylation biomarkers in neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. Amplification of in neuroblastoma is a predictor of poor prognosis. DNA methylation data from the TARGET data matrix were stratified into amplified and non-amplified groups.

In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c).

Nicotinamide-nucleotide adenylyl transferase (Rv2421c) was selected as a potential drug target, because it has been shown, in vitro, to be essential for Mycobacterium tuberculosis growth. It is conserved between mycobacterium species, is up-regulated during dormancy, has a known 3D crystal structure and has no known human homologs. A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject tovirtual ligand screening against the Prestwick Chemical Library and the ZINC database, which yielded 155 potential hit molecules.

Peptides-based therapeutics: Emerging potential therapeutic agents for COVID-19.

SARS-CoV-2 is a positive-sense RNA virus and it is the causative agent of the global COVID-19 outbreak. COVID-19 is similar to the previous outbreaks for instance SARS in 2002-2003 and MERS in 2012. As the peptides have many advantages, peptide-based therapeutics might be one of the possible ways in the development of COVID-19 specific drugs.