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Jihoon Han

@jihoon-han.bsky.social

Synthetic biologist | Bioengineer building molecular tools Postdoc @ Shipman Lab ·@GladstoneInst

Jihoon Han @jihoon-han.bsky.social · 13/10/2026

Finally, we tested DeSTAR on an unseen SARS-CoV-2 N transcript. We built 10 top-ranked sensors and 20 randomly selected ones. Functional sensors (ON/OFF ≥ 2): • Clonal qPCR: 4/10 vs 0/20 • Pooled sequencing: 5/10 vs 2/20 The readouts agreed (ρ = 0.74)!

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Jihoon Han @jihoon-han.bsky.social · 13/10/2026

What drives DeSTAR’s predictions? Feature ablation identified the bottom-stem motif as the key non-redundant feature class. The rule: a weak second stem base pair (bp2) favors activation. Among those sensors, a strong bp3 further improves performance.

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Jihoon Han @jihoon-han.bsky.social · 13/10/2026

Rather than predict absolute activity, we trained DeSTAR to rank sites using pairwise XGBoost. In leave-one-transcript-out tests, its top-ranked sites were more active across all six held-out transcripts. 87% of top-5 picks were among the best 15% (5.8× over random)!

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Jihoon Han @jihoon-han.bsky.social · 13/10/2026

Why do some sites work while others fail? Comparing high- and low-performing sensors revealed a striking pattern: sequence preferences were concentrated at the bottom of the switch stem—not in the single-stranded toehold. This pointed to a shared base-pairing grammar.

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Jihoon Han @jihoon-han.bsky.social · 13/10/2026

To answer this, we tiled six RNAs—phage, viral, and human transcripts—at single-nucleotide resolution. That gave us 7,383 target sites, each tested with 3 DNA barcodes in pooled sequencing assays. Activity varied dramatically, even between neighboring sites!

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Jihoon Han @jihoon-han.bsky.social · 05/10/2026

New since the preprint: ratiometric Detectrons pair an infection-responsive DNA barcode with a constitutive reference barcode in the same strain. Their ratio lets us compare T7 susceptibility across six E. coli genotypes in one pooled assay (Fig. 6).

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Jihoon Han @jihoon-han.bsky.social · 18/02/2026

We then used Detectrons to measure host susceptibility to phage infection. Dual DNA barcoding lets us track phage + host identity simultaneously in one pooled experiment. Sequencing revealed strain-specific susceptibility in a single experiment.

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Jihoon Han @jihoon-han.bsky.social · 18/02/2026

The optimized Detectron design dramatically improved signal strength and specificity, and generalized across multiple phage RNA targets.

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Jihoon Han @jihoon-han.bsky.social · 18/02/2026

We built a large synthetic library (~7,800 variants) and used machine learning to identify structural design rules that improve ON/OFF performance.

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Jihoon Han @jihoon-han.bsky.social · 18/02/2026

Detectrons combine two programmable systems: • toehold switches → RNA sensing • retrons → DNA synthesis RNA trigger → DNA barcode output.

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