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Research PaperResearchia:202609.29024

Continuous Variational Synthesis

Alan N. Amin

Abstract

Biological machine learning was long bottlenecked by the ability to synthesize designed DNA. Variational synthesis models control chemical reactions to physically manufacture quadrillions of designed sequences in DNA. However, training these generative models is challenging: constraints on chemical synthesis can force many parameters into a discrete space, limiting the ability to pre-train and fine-tune. In this article we train free'' variational synthesis models using stochastic gradient desce...

Submitted: September 29, 2026Subjects: Biochemistry; Pharmaceutical Research

Description / Details

Biological machine learning was long bottlenecked by the ability to synthesize designed DNA. Variational synthesis models control chemical reactions to physically manufacture quadrillions of designed sequences in DNA. However, training these generative models is challenging: constraints on chemical synthesis can force many parameters into a discrete space, limiting the ability to pre-train and fine-tune. In this article we train ``free'' variational synthesis models using stochastic gradient descent in continuous space, and then discretize with post-training quantization to impose hardware and wetware constraints. This enables variational synthesis models to satisfy stringent reward criteria, while still synthesizing diverse designs, achieving a strictly dominating quality-diversity Pareto frontier. We demonstrate by training variational synthesis models of enzymes, peptides, antibody CDRH3s, and regulatory DNA elements. In silico performance is maintained in vitro.


Source: arXiv:2609.35083v1 - http://arxiv.org/abs/2609.35083v1 PDF: https://arxiv.org/pdf/2609.35083v1 Original Link: http://arxiv.org/abs/2609.35083v1

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Date:
Sep 29, 2026
Topic:
Pharmaceutical Research
Area:
Biochemistry
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