Machine learning for molecular and materials science

Here we summarize recent progress in machine learning for the chemical sciences. We outline machine-learning techniques that are suitable for addressing research questions in this domain, as well as future directions for the field. We envisage a future in which the design, synthesis, characterization and application of molecules and materials is accelerated by artificial intelligence.</p

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells &lt;sup&gt;1-14&lt;/sup&gt; . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies &lt;sup&gt;15-17&lt;/sup&gt; to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 &lt;sup&gt;+&lt;/sup&gt; T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time

Legume Seed Production Meeting Market Requirements and Economic Impacts

International audienceThe seed is the carrier of the genetic improvements brought about by modern plant breeding, and seed production is carried out in accordance with certification systems to guarantee consistent high quality. In forage legumes, breeding efforts are primarily related to the vegetative development of the plant, although the commercial success of an agronomically superior cultivar is dependent on a reliable supply of competitively priced seed. In seed production of the three most important forage legumes, alfalfa (Medicago sativa L.), white clover (Trifolium repens L.), and red clover (Trifolium pratense L.), crop management techniques are applied to stimulate reproductive development in order to obtain high seed yields. These include a low plant density, manipulation of canopy size to avoid lodging and shading of fruiting organs, synchronization of flowering with pollinating insects as well as controlling pests. High seed yield is correlated to inflorescence density and seed yield per inflorescence, traits which should be selected for in breeding populations as moderate to high heritability has been found. However, seed yield is a genetically complex trait and in the perennial, insect-pollinated forage legumes it is further highly influenced by environmental conditions and crop management factors. Further investigations into the use of plant growth regulators and an improved understanding of the interaction between pollinators and the seed crop might improve future seed yields. There is likely to be an increasing emphasis on the role of forage legumes in producing high-quality meat and milk, combined with the requirement to reduce the environmental footprint of grassland agriculture. A high forage legume seed yield is a prerequisite to meet market requirements for new, improved cultivars and hence achieve the economic impacts of modern plant breeding for a better livelihood and environment