Tegner, J. N. | Search bioRxiv

bioRxiv2023

Foundation Models Meet Imbalanced Single-Cell Data When Learning Cell Type Annotations

With the emergence of single-cell foundation models, an important question arises: how do these models perform when trained on datasets having an imbalance in cell type distribution due to rare cell types or biased sampling? We benchmark three foundation models, scGPT, scBERT, and Geneformer, using skewed single-cell cell-type distribution for cell-type annotation. While all models had reduced performance when challenged with rare cell types, scGPT and scBERT, performed better than Geneformer. Notably, in contrast to scGPT and scBERT, Geneformer uses ordinal positions of the tokenized genes rather than actual raw gene expression values. To mitigate the effect of a skewed distribution, we find that random oversampling, but not random undersampling, improved the performance for all three foundation models. Finally, scGPT, using FlashAttention, has the fastest computational speed, whereas scBERT is more memory-efficient. We conclude that tokenization and data representation are essential areas of research, and new strategies are needed to mitigate the effects of imbalanced learning in single-cell foundation models. Code and data for reproducibility are available at https://github.com/SabbaghCodes/ImbalancedLearningForSingleCellFoundationModels.

bioinformatics↗

bioRxiv2021

DNA transposon expansion is associated with genome size increase in mudminnows

Genome sizes of eukaryotic organisms vary substantially, with whole genome duplications (WGD) and transposable element expansion acting as main drivers for rapid genome size increase. The two North American mudminnows, Umbra limi and U. pygmaea, feature genomes about twice the size of their sister lineage Esocidae (e.g., pikes and pickerels). However, it is unknown whether all Umbra species share this genome expansion and which causal mechanisms drive this expansion. Using flow cytometry, we find that the genome of the European mudminnow is expanded similarly to both North American species, ranging between 4.5-5.4 pg per diploid nucleus. Observed blocks of interstitially located telomeric repeats in Umbra limi suggest frequent Robertsonian rearrangements in its history. Comparative analyses of transcriptome and genome assemblies show that the genome expansion in Umbra is driven by extensive DNA transposon expansion without WGD. Furthermore, we find a substantial ongoing expansion of repeat sequences in the Alaska blackfish Dallia pectoralis, the closest relative to the family Umbridae, which might mark the beginning of a similar genome expansion. Our study suggests that the genome expansion in mudminnows, driven mainly by transposon expansion, but not WGD, occurred before the separation into the American and European lineage. Significance StatementNorth American mudminnows feature genomes about twice the size of their sister lineage Esocidae (e.g., pikes and pickerels). However, neither the mechanism underlaying this genome expansion, nor whether this feature is shared amongst all mudminnows is currently known. Using cytogenetic analyses, we find that the genome of the European mudminnow also expanded and that extensive chromosome fusion events have occurred in some Umbra species. Furthermore, comparative genomics based on de-novo assembled transcriptomes and genome assemblies, which have recently become available, indicates that DNA transposon activity is responsible for this expansion.

evolutionary biology↗