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Balla, K.

Publications and source records attributed to Balla, K..

3 recordsLinked to original sources

RNAquarium: an archive-scale atlas of zebrafish gene expression coupled with pan-taxonomic profiling reveals diverse viral drivers of transcriptomic states

Zebrafish RNA-seq studies span diverse developmental, physiological, and disease contexts, yet most analyses remain confined to individual experiments and disregard the non-zebrafish component of the data. We present RNAquarium, a scalable framework for joint transcriptomic and metatranscriptomic analysis of RNA-seq data and apply it to all publicly available zebrafish RNA-seq datasets in the Sequence Read Archive. This resource captures transcriptomic structure across development and tissues, reveals diverse microbial and viral associations, and identifies previously undescribed zebrafish viruses including a close relative of human influenza B virus linked to distinct host transcriptional states. We further demonstrate that archive-scale transcriptomes can support foundation-model training and prediction of infection-associated transcriptomic signatures. RNAquarium provides an open framework and interactive portal for exploring the breadth of zebrafish gene expression patterns and associated taxa profiled across a large re-search community and establishes a generalizable strategy for integrating transcriptomic and metatranscriptomic analyses across the diversity of life represented in public sequencing archives.

genomics↗

Zebrahub - Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors

Elucidating the developmental processes of organisms requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate mapping experiments. To demonstrate the versatility of our multi-modal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, Zebrahub, is a foundational resource for studying developmental processes at both transcriptional and spatiotemporal levels, providing researchers with an integrated approach to exploring and analyzing the complexities of cellular lineages during zebrafish embryogenesis.

developmental biology↗

Natural variation in the C. elegans autophagy response and clearance of intracellular microsporidia

Natural genetic variation can determine the outcome of an infection, and often reflects the co-evolutionary battle between hosts and pathogens. We previously found that a natural variant of the nematode Caenorhabditis elegans from Hawaii (HW) has increased resistance against natural microsporidian pathogens in the Nematocida genus, when compared to the standard laboratory strain of N2. In particular, HW animals can clear infection, while N2 animals cannot. In addition, HW animals have lower levels of intracellular colonization of Nematocida compared to N2. Here we investigate how this natural variation in resistance relates to autophagy. We found that there is much better targeting of autophagy-related machinery to parasites under conditions where they are cleared. In particular, ubiquitin targeting to Nematocida cells correlates very well with their subsequent clearance in terms of timing, host strain and age, as well as Nematocida species. Furthermore, clearance correlates with targeting of the LGG-2/LC3 autophagy protein to parasite cells, with HW animals having much more efficient targeting of LGG-2 to parasite cells than N2 animals. Surprisingly, however, we found that lgg-2 is not required to clear infection. Instead we found that loss of lgg-2 leads to increased intracellular colonization in the HW background, although interestingly, it does not affect colonization in the N2 background. Altogether our results suggest that there is natural genetic variation in an lgg-2-dependent process that regulates intracellular levels of microsporidia at a very early stage of infection prior to clearance.

immunology↗