12/1/22 |
Jamshed Khan |
CBCB/Patro Lab |
Drinking from the firehose through compact de Bruijn graphs: dealing with high-throughput genomic data for downstream analysis
Abstract: The de Bruijn graph is a key data structure in modern computational genomics, and its compacted variant resides upstream of many genomic analyses. These graphs are increasingly used as sequence indices for short- and long-read alignment. Also, as we sequence and assemble a greater diversity of genomes, the colored compacted de Bruijn graph is being used more and more as the basis for efficient methods to perform comparative genomic analyses on these genomes. As the quantity of genomic data grows rapidly, the construction of these graphs often forms a computational bottleneck. We present Cuttlefish 2, significantly advancing the state-of-the-art for this problem. On a commodity server, it reduces the graph construction time for 661K bacterial genomes, of size 2.58Tbp, from 4.5 days to 17–23 h; and it constructs the graph for 1.52Tbp white spruce reads in approximately 10 h, while the closest competitor requires 54–58 h, using considerably more memory. Then we briefly propose some opportunities of using these compact graphs to index large-scale sequence collections.
Cuttlefish 2 is implemented in C++17, and is released under the BSD 3-Clause “New” or “Revised” License. The latest source code is available at: https://github.com/COMBINE-lab/cuttlefish. It is also available through conda: https://anaconda.org/bioconda/cuttlefish. |
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12/8/22 |
Renee Ti Chou |
CBCB/Cummings Lab |
Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery
Abstract: Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We developed a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) was conjugated to brimonidine, an intraocular pressure (IOP)-lowering drug that is prescribed for three times per day topical dosing, IOP reduction was observed for up to 18 days after a single intracameral HR97-brimonidine injection in rabbits. Further, the cumulative IOP-lowering effect was increased ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond. |
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