Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this “AstroPath” whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti–programmed cell death-1 (PD-1)–based therapy, including CD163+PD-L1– myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti–PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.

The nature of the psychological processes that underlie the Gestalt principles of grouping by proximity and grouping by similarity is examined. Similarity was defined relative to the principles of grouping by common colour and grouping by common shape. Subjects were presented with displays comprising a row of seven coloured shapes and were asked to rate the degree to which the central target shape grouped with either the right or the left flanking shapes. Across the displays the proximal and featural relationships between the target and flankers were varied. These ratings reflected persuasive effects of grouping by proximity and common colour; there was only weak evidence for grouping by common shape. Nevertheless, both common colour and common shape were shown to override grouping by proximity, under certain conditions. The data also show that to understand how the Gestalt principles operate it appears necessary to consider processes that operate within and between groups of elements that are initially identified on the basis of proximity. Whether such groups survive further analysis depends critically on the featural content of the constituent elements.

When computing alignments of DNA sequences to a large genome, a key element in achieving high processing throughput is to prioritize locations in the genome where high-scoring mappings might be expected. We formulated this task as a series of list-processing operations that can be efficiently performed on graphics processing unit (GPU) hardware.We followed this approach in implementing a read aligner called Arioc that uses GPU-based parallel sort and reduction techniques to identify high-priority locations where potential alignments may be found. We then carried out a read-by-read comparison of Arioc’s reported alignments with the alignments found by several leading read aligners. With simulated reads, Arioc has comparable or better accuracy than the other read aligners we tested. With human sequencing reads, Arioc demonstrates significantly greater throughput than the other aligners we evaluated across a wide range of sensitivity settings. The Arioc software is available at . It is released under a BSD open-source license.

On being shown the names of two towns geography students determined whether one of the towns was north (say) of the other. Reaction time decreased as the distance between the towns increased. This finding was explained by supposing that subjects attempt to make inferences (about whether one town is north of another) by first accessing stored information that specifies a town's location only crudely; when this is insufficient to make the relevant inference more finely discriminating information is accessed. The explanation was supported in a second experiment: when one town was Scottish and the other English, reaction times were shorter than when both were English. This result was predicted from the assumption that the information first accessed specifies which country a town lies in: when one town is Scottish and the other English, this information can be used to make the correct inference without further specification of location (since all Scottish towns are north of all English towns), whereas when both towns are English further information must be accessed. Control conditions showed the result was not due merely to a greater familiarity with Scottish towns. The explanation was discussed in relation to accounts of reaction times obtained when other characteristics (e.g. size) of named objects are compared.

DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.