Abduragim Shtanchaev

Aya Laajil, Abduragim Shtanchaev, Sajan Muhammad et al.

Designing mRNA sequences is a major challenge in developing next-generation therapeutics, since it involves exploring a vast space of possible nucleotide combinations while optimizing sequence properties like stability, translation efficiency, and protein expression. While Generative Flow Networks are promising for this task, their training is hindered by sparse, long-horizon rewards and multi-objective trade-offs. We propose Curriculum-Augmented GFlowNets (CAGFN), which integrate curriculum learning with multi-objective GFlowNets to generate de novo mRNA sequences. CAGFN integrates a length-based curriculum that progressively adapts the maximum sequence length guiding exploration from easier to harder subproblems. We also provide a new mRNA design environment for GFlowNets which, given a target protein sequence and a combination of biological objectives, allows for the training of models that generate plausible mRNA candidates. This provides a biologically motivated setting for applying and advancing GFlowNets in therapeutic sequence design. On different mRNA design tasks, CAGFN improves Pareto performance and biological plausibility, while maintaining diversity. Moreover, CAGFN reaches higher-quality solutions faster than a GFlowNet trained with random sequence sampling (no curriculum), and enables generalization to out-of-distribution sequences.

Arip Asadulaev, Semyon Semenov, Abduragim Shtanchaev et al.

Modern continuous-time generative models often induce V-shaped transport: each sample travels independently along nearly straight trajectories from prior to data, overlooking shared structure. We introduce Y-shaped generative flows, which move probability mass together along shared pathways before branching to target-specific endpoints. Our formulation is based on novel velocity-powered objective with a sublinear exponent (between zero and one). this concave dependence rewards joint and fast mass movement. Practically, we instantiate the idea in a scalable neural ODE training objective. On synthetic, image, and biology datasets, Y-flows recover hierarchy-aware structure, improve distributional metrics over strong flow-based baselines, and reach targets with fewer integration steps.