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Stormo, G. D.

Publications and source records attributed to Stormo, G. D..

2 recordsLinked to original sources

Deep unfolded convolutional dictionary learning for motif discovery

We present a principled representation learning approach based on convolutional dictionary learning (CDL) for motif discovery. We unroll an iterative algorithm that optimizes CDL as a forward pass in a neural network, resulting in a network that is fully interpretable, fast, and capable of finding motifs in large datasets. Simulated data show that our network is more sensitive and specific for discovering binding sites that exhibit complex binding patterns than popular motif discovery methods such as STREME and HOMER. Our network reveals statistically significant motifs and their diverse binding modes from the JASPAR database that are currently not reported.

bioinformatics↗

Autoregulation of Many Yeast Ribosomal Proteins Discovered by Efficient Search for Feedback Regulation

Post-transcriptional autoregulation of gene expression is common in bacterial systems but many fewer examples are known in eukaryotes. We used the yeast collection of genes fused to GFP as a rapid screen for examples of feedback regulation in ribosomal proteins by overexpressing a non-regulatable version of a gene and observing the effects on the expression of the GFP-fused version. We tested 95 ribosomal protein genes and found that 21 of them showed at least a three-fold repression. Two genes, RPS22B and RPL1B, showed over a 10-fold repression. In both cases the cis-regulatory segment resides in the 5 UTR of the gene as shown by placing that segment of the mRNA upstream of GFP alone and demonstrating it is sufficient to cause repression of GFP when the protein is over-expressed. Further analyses showed that the intron in the 5 UTR of RPS22B is required for regulation, presumably because the protein inhibits splicing that is necessary for translation. The 5 UTR of RPL1B contains a sequence and structure motif that is conserved in the binding sites of Rpl1 orthologs from bacteria to mammals, and mutations within the motif eliminate repression.

systems biology↗