Autonomous, multi-property-driven molecular discovery: from predictions to measurements and back

A closed-loop, autonomous molecular discovery platform driven by integrated machine learning tools was developed to accelerate the design of molecules with desired properties. Two case studies are demonstrated on dye-like molecules, targeting absorption wavelength, lipophilicity, and photo-oxidative stability. In the first, the platform experimentally realized 312 unreported molecules across three automatic iterations of molecular design-make-test-analyze cycles while exploring the structure–function space of four rarely reported scaffolds. In each iteration, the property-prediction models which guided the exploration learned the structure–property space of diverse inexpensive scaffold derivatives realized through using multi-step syntheses. Conversely, the second study exploited property models trained on a chemical space with pre-existing examples to discover 6 top-performing molecules within the structure-property space. By closing the molecular discovery cycle of prediction, synthesis, measurement, and model retraining, the platform demonstrates the potential for integrated platforms to automatically understand a local chemical space and discover functional molecules

Comparative analysis of metazoan chromatin organization.

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function