Biology subjects

Bakker, S.

Publications and source records attributed to Bakker, S..

4 recordsLinked to original sources

bioRxiv2025

Delineating inter- and intra-antibody repertoire evolution with AntibodyForests

MotivationThe rapid advancements in immune repertoire sequencing, powered by single-cell technologies and artificial intelligence, have created unprecedented opportunities to study B cell evolution at a novel scale and resolution. However, fully leveraging these data requires specialized software capable of performing inter- and intra-repertoire analyses to unravel the complex dynamics of B cell repertoire evolution during immune responses. ResultsHere, we present AntibodyForests, software to infer B cell lineages, quantify inter- and intra-antibody repertoire evolution, and analyze somatic hypermutation using protein language models and protein structure. Availability and implementationThis R package is available on CRAN (1) and Github at https://github.com/alexyermanos/AntibodyForests, a vignette is available at https://cran.case.edu/web/packages/AntibodyForests/vignettes/AntibodyForests_vignette.html

bioinformatics↗

bioRxiv2024

Effects of environmental and individual variation on time patterns of extinction in small experimental populations.

Predicting the fate of small populations is essential in ecology, epidemiology and conservation biology. Small populations can go extinct quickly or can develop into large established populations. These can still go extinct through demographic stochasticity, especially when declines in mean population size or large size fluctuations drive them into an extinction vortex. Individual life stage and environmental conditions experienced by founding individuals are two factors expected to determine the fate of small populations. When they dont go extinct, life stage effects are expected to wash out. Initial environmental differences equally so, unless differences in environmental conditions continue to occur. We used the parthenogenetic Collembola Folsomia candida to investigate such effects in a crossed treatment on 290 replicate populations, each initiated with a single individual. Populations were initiated with founders of three different life stages and subjected to four levels of culling. Their extinction times were recorded in a period of up to 41 weeks after initiation. We fitted the parameters of an age-structured multi-type branching process model to extinction rates observed in the first weeks after initiation. As predicted by the model, extinction probabilities early in the experiment increased with the level of culling. Extinction probabilities were larger in populations founded by non-reproducing individuals. These decreased over time, presumably because of the onset of reproduction. In established populations, extinction probabilities increased with culling level and the effects of the founder stage disappeared, except for a late increase in extinction probability in populations founded by newborns. This increase was not expected and forced us to reconsider when transient effects of the initial state would end. We hypothesize that it is due to effects of size-structured competition in this system. The results show that predictors of extinction probability can be shared between small and established populations. Transient dynamics of extinction risk can be long, with phases even mimicking a stationarity followed by the onset of an extinction vortex.

evolutionary biology↗

bioRxiv2024

FungAMR: A comprehensive portrait of antimicrobial resistance mutations in fungi

Antimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, we performed a thorough manual curation of published AMR mutations in fungal pathogens to produce the FungAMR reference dataset. A total of 501 papers were curated, leading to 35,792 mutation entries all classified with the degree of evidence that supports their role in resistance. FungAMR covers 95 species, 246 genes and 208 drugs. We combined variant effect predictors with FungAMR resistance mutations and showed that these tools could be used to help predict the potential impact of mutations on AMR. Additionally, a comparative analysis among species revealed a high level of convergence in the molecular basis of resistance, highlighting some potentially universal resistance mutations. The analysis also showed that a significant number of resistance mutations lead to cross-resistance within antifungals of a class, as well as between classes for certain mutated genes. The acquisition of fungal resistance in the clinic and the field is an urging concern. Finally, we provide a computational tool, ChroQueTas, that leverages FungAMR to screen fungal genomes for AMR mutations. These resources are anticipated to have great utility for researchers in the fight against antifungal resistance.

microbiology↗

bioRxiv2024

Resolving a neonatal intensive care unit outbreak of methicillin-resistant Staphylococcus aureus to the SNV level using Oxford Nanopore simplex reads and HERRO error correction

ObjectivesOur laboratory began prospective genomic surveillance for healthcare-associated organisms in 2022 using Oxford Nanopore Technologies (ONT) sequencing as a standalone platform. This has permitted the early detection of outbreaks but has been insufficient for single-nucleotide variant (SNV)-level analysis due to lower read accuracy than Illumina sequencing. This study aimed to determine whether Haplotype-aware ERRor cOrrection (HERRO) of ONT data could permit high-resolution comparison of outbreak isolates. MethodsWe used ONT simplex reads from isolates involved in a recent outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in our neonatal unit. The raw sequence data were re-basecalled and adapter-trimmed using Dorado v0.7.0. The simplex reads then underwent HERRO correction. The resulting genome assemblies and phylogenies were compared with previous analyses (using Dorado v0.3.4, no HERRO correction and data generated by Illumina sequencing). ResultsFive of nine outbreak isolates were included in the analysis. The remaining four isolates had insufficient read lengths (N50 values <10,000 bp) and did not provide complete chromosome coverage after HERRO correction. The average chromosome sequencing depth for nanopore data was 147x (range: 44-220x) with an average read N50 of 12,215 bp (interquartile range (IQR): 11,439-12,711 bp). The median pairwise SNV distance between outbreak isolates from the original investigation was 51 SNVs (range: 40-68), which decreased to 3 SNVs (range: 1-15) with HERRO correction. Illumina sequencing generated a median SNV distance of 2 (range: 0-13). The resulting standalone ONT HERRO-corrected phylogeny was almost indistinguishable from the standalone Illumina-generated phylogeny. ConclusionsThe addition of HERRO correction meant isolates from this MRSA outbreak could be resolved to a level on par with Illumina sequencing. ONT data following HERRO correction represents a viable standalone option for high-resolution genomic analysis of hospital outbreaks, provided sufficient read lengths can be generated.

genomics↗