Biology subjects

Gibb, A.

Publications and source records attributed to Gibb, A..

3 recordsLinked to original sources

bioRxiv2025

FAVABEAN and FALAPhyl: Open-Source Pipelines for Scalable 16s rRNA Microbiome Data Processing and Visualization

Reproducible and scalable analysis of 16S rRNA amplicon sequencing data remains a persistent challenge in microbiome research due to the complexity of available tools, incompatibilities between platforms, and the need for extensive bioinformatics expertise. We developed two containerized workflows--FAVABEAN (Fast Amplicon Variant Annotation, Binning, Error-correction And ANalysis) and FALAPhyl (Forays into Automating Laborious Analyses of Phylogeny)--to address these challenges. FAVABEAN and FALAPhyl are Snakemake-based pipelines designed for flexible execution across local, cluster, and cloud environments. FAVABEAN automates preprocessing, ASV inference, and taxonomic assignment using DADA2 and FIGARO, including primer averaging when samples are sequenced with multiple primers. FALAPhyl supports downstream analysis including alpha/beta diversity, network analysis, and differential abundance testing, with integrated provenance tracking. We validated both pipelines using three case studies involving oral microbiome datasets. In Case Study 1, we compared oral microbiota across family members and niches, showing primer-dependent variability in ASV-based similarity and minimal reseeding from familial sources after prophylaxis. Case Study 2 analyzed dental aerosol samples, revealing no significant microbial differences between pre-, intra-, and post-procedure air. Case Study 3, a randomized trial of a nitrate mouthrinse, demonstrated no significant microbiome shifts, highlighting oral microbial stability. FALAPhyls integration of DAtest enabled empirical evaluation of multiple statistical tests, aiding robust differential abundance inference. FAVABEAN and FALAPhyl offer a reproducible, automated solution for 16S rRNA amplicon data analysis. Their modular design, containerization, and provenance tracking enhance accessibility and scientific rigor in microbiome research.

bioinformatics↗

bioRxiv2022

A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during ageing and in Alzheimer's disease

Synapse loss strongly correlates with cognitive decline in Alzheimers Disease (AD), but the underlying mechanisms are poorly understood. Studies suggest that deficient Wnt signalling, a pathway required for neuronal connectivity, contributes to synapse dysfunction and loss in AD. Consistent with this idea, a variant of Lrp6, (Lrp6-val), which confers reduced Wnt signalling, has been linked to late onset AD. However, the impact of Lrp6-val on synapses in the healthy and AD brain has not been examined. Using CRISPR/Cas9 genome editing, we generated a novel knock-in mouse model carrying this Lrp6 variant to study its role in synaptic integrity. Lrp6-val mice develop normally and do not exhibit morphological brain abnormalities. Hippocampal neurons from Lrp6-val mice do not respond to Wnt7a, a Wnt ligand that promotes synaptic assembly through the Frizzled-5 (Fz5) receptor. Activation of the Wnt pathway by Wnt ligands leads to the formation of a complex between LRP6 and Fz5. In contrast, LRP6-Val impairs the formation of the LRP6-Fz5 complex elicited by Wnt7a, as detected by proximity ligation assay (PLA). We demonstrate that Lrp6-val mice exhibit structural and functional synaptic defects that become more pronounced with age, consistent with decreased canonical Wnt signalling during ageing. To investigate the contribution of this variant to AD, Lrp6-val mice were crossed to hAPPNL-G-F/NL-G-F (NL-G-F), a knock-in AD mouse model. The presence of the Lrp6-val variant significantly exacerbates synapse loss around amyloid-{beta} plaques in NL-G-F mice. Our findings uncover a novel role for the Lrp6-val variant in synapse vulnerability during ageing and its contribution to synapse degeneration in AD.

neuroscience↗

bioRxiv2017

Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.

biophysics↗