Biology subjects

Veal, A.

Publications and source records attributed to Veal, A..

4 recordsLinked to original sources

bioRxiv2026

The Drosophila Secretome

Secreted proteins are synthesized within the cell and actively transported outside, where they contribute to development, physiology, immunity, and cellcell communication. In Drosophila melanogaster, many secreted signaling pathways are evolutionarily conserved, making this species a powerful model for studying human development, cancer, neurobiology, and immune regulation. To assemble the Drosophila secretome, we systematically analyzed all fly protein sequences with computational tools, integrating FlyBase, UniProt and Gene Ontology annotations, and incorporating large-scale proteomics datasets. We identified 4,831 genes encoding putative secreted proteins, assigned confidence scores based on the type and strength of supporting evidence, and generated an online resource (www.flyrnai.org/apps/fly_secretome/) for exploring these data. Comparison with the human secretome shows that 54% of Drosophila secretome genes are conserved in the human genome and of these, 83% are annotated as secreted in human. In addition, comparison with Drosophila single-cell transcriptomic data revealed that secreted proteins are more tissue-specific than other genes. Finally, we demonstrate the utility of this resource by analyzing changes in expression of genes encoding putative secreted proteins during aging based on snRNA-seq datasets from the Aging Fly Cell Atlas.

genetics↗

bioRxiv2026

Genome-wide CRISPR knockout cell screening platform for the disease vector tick species Ixodes scapularis

The black legged tick, Ixodes scapularis, is a vector of the bacterium that causes Lyme disease and several other illnesses, including anaplasmosis, babesiosis, and tick-borne encephalitis. Although high-quality genome annotations are available for I. scapularis, functional understanding of I. scapularis genes is limited. To address this, we developed a platform for genome-wide CRISPR-Cas9 knockout screening in I. scapularis cells. To evaluate the platform, we performed a screen to identify genes associated with cellular fitness, and screens for resistance to treatment with copper chloride, Antimycin A, or Destruxin A (DA), a cyclic hexadepsipeptide produced by the pathogenic fungus Metarhizium anisopliae. In each case, the screens implicate specific sets of conserved and non-conserved I. scapularis genes in relevant cellular functions, providing the first experimental evidence of function for a large set of I. scapularis genes. Altogether, in this first-of-its-kind effort for the arthropod subclass Acari, we present an unbiased genome-wide CRISPR-Cas9 knockout cell screening platform, related resources, and datasets that will be broadly useful to efficiently uncover cellular functions of I. scapularis genes.

genetics↗

bioRxiv2026

FlyPredictome: A structural atlas of predicted protein-protein interactions in Drosophila

Protein-protein interactions (PPIs) are fundamental to cellular function. Yet most Drosophila PPIs remain structurally uncharacterized despite the wealth of genetic and biochemical data available for this organism. Here we present FlyPredictome, a structural interactome based on 1.5 million pairwise AlphaFold-Multimer predictions. Using a local confidence metric performing robustly on interactions involving flexible and disordered proteins, we systematically assess experimentally reported Drosophila PPIs and predict direct binding interfaces at residue-level resolution. Testing their functional relevance, we find that phenotype-associated missense mutations are enriched at predicted interaction interfaces. Building on these predictions, we construct an evidence-supported PPI network, revealing modular organization from signaling pathways to individual protein complexes. We further predict higher-order complexes for nearly 400 of these modules with AlphaFold3, matching available cryo-EM structures and extending to unresolved assemblies. Fly-Predictome is available as an open, interactive database that maps interactions to residue-level binding surfaces, providing a structural foundation for interaction discovery in Drosophila.

bioinformatics↗

bioRxiv2025

TF2TG: an online resource mining the potential gene targets of transcription factors in Drosophila

Sequence-specific transcription factors (TFs) are key regulators of many biological processes, controlling the expression of their target genes through binding to the cis-regulatory regions such as promoters and enhancers. Each TF has unique DNA binding site motifs, and large-scale experiments have been conducted to characterize TF-DNA binding preferences. However, no comprehensive resource currently integrates these datasets for Drosophila. To address this need, we developed TF2TG ("transcription factor to target gene"), a comprehensive resource that combines both in vitro and in vivo datasets to link transcription factors (TFs) to their target genes based on TF-DNA binding preferences along with the protein-protein interaction data, tissue-specific transcriptomic data, and chromatin accessibility data. Although the genome offers numerous potential binding sites for each TF, only a subset is actually bound in vivo, and of these, only a fraction is functionally relevant. For instance, some TFs bind to their specific sites due to synergistic interactions with other factors nearby. This integration provides users with a comprehensive list of potential candidates as well as aids users in ranking candidate genes and determining condition-specific TF binding for studying transcriptional regulation in Drosophila.

bioinformatics↗