The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genetic programming for kernel-based learning with co-evolving subsets selection

Abstract. Support Vector Machines (SVMs) are well-established Machine Learning (ML) algorithms. They rely on the fact that i) linear learning can be formalized as a well-posed optimization problem; ii) nonlinear learning can be brought into linear learning thanks to the kernel trick and the mapping of the initial search space onto a high dimensional feature space. The kernel is designed by the ML expert and it governs the efficiency of the SVM approach. In this paper, a new approach for the automatic design of kernels by Genetic Programming, called the Evolutionary Kernel Machine (EKM), is presented. EKM combines a well-founded fitness function inspired from the margin criterion, and a co-evolution framework ensuring the computational scalability of the approach. Empirical validation on standard ML benchmark demonstrates that EKM is competitive using state-of-the-art SVMs with tuned hyper-parameters.