Search for: All records

Computer-aided synthesis planning (CASP) algorithms have demonstrated expertlevel abilities in planning retrosynthetic routes to molecules of low to moderate complexity. However, current search methods assume the sufficiency of reaching arbitrary building blocks, failing to address the common real-world constraint where using specific molecules is desired. To this end, we present a formulation of synthesis planning with starting material constraints. Under this formulation, we propose Double-Ended Synthesis Planning (DESP), a novel CASP algorithm under a bidirectional graph search scheme that interleaves expansions from the target and from the goal starting materials to ensure constraint satisfiability. The search algorithm is guided by a goal-conditioned cost network learned offline from a partially observed hypergraph of valid chemical reactions. We demonstrate the utility of DESP in improving solve rates and reducing the number of search expansions by biasing synthesis planning towards expert goals on multiple new benchmarks. DESP can make use of existing one-step retrosynthesis models, and we anticipate its performance to scale as these one-step model capabilities improve. 

Abstract Analysis of single-cell datasets generated from diverse organisms offers unprecedented opportunities to unravel fundamental evolutionary processes of conservation and diversification of cell types. However, interspecies genomic differences limit the joint analysis of cross-species datasets to homologous genes. Here we present SATURN, a deep learning method for learning universal cell embeddings that encodes genes’ biological properties using protein language models. By coupling protein embeddings from language models with RNA expression, SATURN integrates datasets profiled from different species regardless of their genomic similarity. SATURN can detect functionally related genes coexpressed across species, redefining differential expression for cross-species analysis. Applying SATURN to three species whole-organism atlases and frog and zebrafish embryogenesis datasets, we show that SATURN can effectively transfer annotations across species, even when they are evolutionarily remote. We also demonstrate that SATURN can be used to find potentially divergent gene functions between glaucoma-associated genes in humans and four other species.