Biology subjects

Ibeh, N.

Publications and source records attributed to Ibeh, N..

4 recordsLinked to original sources

bioRxiv2024

Profiling genetically driven alternative splicing across the Indonesian Archipelago

One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterised across human populations, and it is unclear how genetic and environmental variation contribute to alternative splicing. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using a hierarchical event-based statistical model, we detected over 1,000 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci; sQTLs), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity revealed that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute towards elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world.

genomics↗

bioRxiv2023

De novo transcriptome assembly and genome annotation of the fat-tailed dunnart (Sminthopsis crassicaudata)

Marsupials exhibit highly specialized patterns of reproduction and development, making them uniquely valuable for comparative genomics studies with their sister lineage, eutherian (also known as placental) mammals. However, marsupial genomic resources still lag far behind those of eutherian mammals, limiting our insight into mammalian diversity. Here, we present a series of novel genomic resources for the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-like marsupial that, due to its ease of husbandry and ex-utero development, is emerging as a laboratory model. To enable wider use, we have generated a multi-tissue de novo transcriptome assembly of dunnart RNA-seq reads spanning 12 tissues. This highly representative transcriptome is comprised of 2,093,982 assembled transcripts, with a mean transcript length of 830 bp. The transcriptome mammalian BUSCO completeness score of 93% is the highest amongst all other published marsupial transcriptomes. Additionally, we report an improved fat-tailed dunnart genome assembly which is 3.23 Gb long, organized into 1,848 scaffolds, with a scaffold N50 of 72.64 Mb. The genome annotation, supported by assembled transcripts and ab initio predictions, revealed 21,622 protein-coding genes. Altogether, these resources will contribute greatly towards characterizing marsupial biology and mammalian genome evolution.

genomics↗

bioRxiv2019

Episodic diversifying selection and intragenomic interactions shape the evolution of DNA and RNA viruses

Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, topped by single-stranded (ss) RNA viruses, while double-stranded (ds) DNA viruses have rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is less well documented. To understand how these two processes affect viral evolution, we systematically surveyed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus type and which functions show evidence for episodic diversifying selection and correlated evolution. We show that while evidence for selection is mostly found in single stranded viruses, and correlated evolution is more prevalent in DNA viruses, the genes that are affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that selection alone does not explain the whole evolutionary --and epidemiological-- potential of viruses.

evolutionary biology↗

bioRxiv2016

Estimation of sub-epidemic dynamics by means of Sequential Monte Carlo Approximate Bayesian Computation: an application to the Swiss HIV Cohort Study

Our ability to accurately infer transmission patterns of infectious diseases is critical to monitor both their spread and the efficacy of public health policies. The use of phylogenetic methods for the reconstruction of viral ancestral relationships has garnered increasing interest, particularly in the characterization of HIV epidemics and sub-epidemics. In the case of this virus, the Swiss HIV Cohort Study (SHCS) contains a wide breadth of genomic data that have been widely used as a means of applying such methods. However, current approaches for quantifying the epidemiological dynamics of diseases are computationally intensive, and fail to scale well with this magnitude of data. To address this issue, we re-implement an Approximate Bayesian Computation (ABC) approach based on sequential Monte Carlo (SMC). By means of simulations, we demonstrate that our implementation is capable of inferring key epidemiological parameters of the Swiss HIV epidemic accurately, and that sampling intensity has no significant effect on the accuracy of our estimates. Applied to a subset of HIV sequences from the SHCS, we show that we can distinguish sub-epidemics that are circulating in culturally distinct Swiss regions. Given these findings, we propose that ABC-SMC samplers will allow us to evaluate the impact of new public health policies, such as the implementation of a needle exchange program in the case of HIV, based on genetic data sampled before and after the implementation of a new policy.

evolutionary biology↗