bioRxiv Science⌕ Search

Biology subjects

Oualline, G.

Publications and source records attributed to Oualline, G..

2 recordsLinked to original sources

Bypassing Current Biosecurity Screens with AI Designed Proteins and Closing the Gap with Edge-AI Functional Screening

DNA synthesis machines are vital tools in medicine and research, but they can be misused to produce sequences which are transcribed and translated to produce toxic proteins. Synthesis providers may screen orders for dangerous sequences, but most screening software performs sequence-based alignment, which is vulnerable to AI redesign attacks. Additionally, software-only synthesis screening requires the operator of the machine to be trusted. We present Capiti, an edge-deployed screening system that runs with no internet connection, listens directly to a synthesizer's valve control signals, and aborts a run when it detects incipient pathogenic function. Rather than performing sequence alignment, Capiti is specifically trained to recognize fold. ProteinMPNN was used to generate putatively functional variants of known pathogenic proteins, and a CNN was trained to separate them from active-site knockouts, scrambles, and decoys. We release two models, Capiti-E (known pathogenic proteins) and Capiti-C (resistance genes for antibiotics of last resort), alongside emusynth, a DNA synthesizer emulator. On our test sets, IBBIS commec and SeqScreen incorrectly passed 18.5% and 44.7% of putatively functional pathogenic variants respectively; Capiti passed 0.24%.

bioinformatics↗

Approximate local alignment via chained MEM divergence estimation for detecting horizontal gene transfer

Local alignment tools struggle at querying against thousands of bacterial genomes, because the reference indexes are memory-intensive and base-level dynamic programming is slow. We present alamem (https://github.com/yunwilliamyu/alamem), an approximate local aligner that streams unprocessed reference databases and estimates average nucleotide identity (ANI) from Maximal-Exact-Match (MEM) chaining statistics. Alamem can query a bacterial genome against >85,000 prokaryotic genomes in under 30 seconds (with multithreading) using 4 GB of memory, making it over 16x faster and 21x more memory-efficient than existing local aligners using their default running modes. On top of alamem, we built alasight (https://github.com/graceoualline/alasight) for detecting signatures of horizontal gene transfer (HGT) by finding pairs of alamem hits to divergent genomes. Alasight achieves over an order of magnitude better sensitivity on data from real bovid microbiomes than existing mobile genetic element-detection software and provides depth and sparsity information supporting each putative HGT region.

bioinformatics↗