The Drosophila Secretome

Key results

1. ShownThe putative fly secretome holds 5,280 protein-coding genes. 1,802 high-confidence genes come from curated annotation or experimental data. 3,478 low-confidence genes come from computational predictions (signal peptides, predicted cell-surface proteins) or Vesiclepedia. Each gene also gets an evidence-based score.

   Four curated sources gave 1,802 unique genes: 1,130 (63%) from a single source and 672 (37%) from two or more. Of these, 1,569 (87%) had at least one isoform with a predicted signal peptide. Another 2,509 unannotated genes had predicted signal peptides, and Vesiclepedia added 451 genes. · Assembly of a Drosophila secretome database

2. ShownSecretome genes have a human ortholog less often than other fly genes, and the gap remains after stratifying by protein length. Most of the conserved secretome genes have orthologs that are annotated as human secreted genes.

   DIOPT v10 (high/moderate): 56% (2,955 of 5,280) of secretome genes have a human ortholog vs 79% of non-secretome genes; 2,402 (81%) of these map to a 6881-gene human secretome reference. Proteins >200 amino acids: 69% vs 83%; 200 amino acids or shorter: 31% vs 60%. Short proteins (<200 amino acids): 28% of secreted vs 19% of other genes. · 1.) Conservation

3. SuggestedIn Fly Cell Atlas (FCA) pseudo-bulk data, secretome genes fall into tissue-specific categories more often than the rest of the proteome, and into 'Expressed in All' less often. Uncharacterized (CG) secretome genes are more tissue-restricted than characterized ones.

   250 cell types were pooled into 14 systems as counts-per-million (CPM) pseudo-bulk and classed with the Human Protein Atlas 5-fold scheme; the text does not give proportions for secretome vs rest. Uncharacterized vs characterized secretome genes: tissue-specific 22% vs 14%, expressed in all 4% vs 24%, not detected 40% vs 18%. CG genes make up 44% of the secretome vs 40% of other genes. · 2.) Tissue expression

4. SuggestedIn Aging Fly Cell Atlas body data, high-confidence secreted genes change expression between 70-day and 5-day flies more often than other genes, mostly downward. In hemocytes, however, more immune genes go up than down.

   Per-system comparison, adjusted p < 0.05 and |log2 fold change| > 1: 39% of high-confidence secreted genes are down-regulated in one or more tissues vs 22% of non-secreted genes, and 49% of them are differentially expressed vs 36% of all protein-coding genes. Down-regulated secreted genes outnumber up-regulated ones, often by 5–15 fold; female reproduction and gut have the most. · Global expression changes in the secretome…; Figure legends

5. ShownA public web portal supports single-gene and batch lookup and lets users browse genes filtered by FCA expression. It links each gene to its evidence, predictions, proteomics, orthologs, candidate receptors and RNAi stocks. Existing RNAi lines cover most secretome genes.

   The portal has a 13-tab menu: bulk RNA-seq (modENCODE, FlyAtlas2), scRNA-seq pseudo-bulk, markers and differential expression, a proteomics-based secretion destination, DIOPT orthologs, PANGEA gene sets, FlyPhoneDB/FlyPredictome receptors and RNAi stocks. VDRC, TRiP and NIG RNAi lines cover 92% of secretome genes, including 85% of 2,208 uncharacterized ones; UAS-cDNA stocks cover 33% and 15% respectively. · 2.) Tissue expression; Drosophila Secretome online resource