Lung Tissue Multilayer Network Analysis Uncovers the Molecular Heterogeneity of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics. We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD.

Lung immune signatures define two groups of end-stage IPF patients.

Background: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.

Methods: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26).

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes.

Optimized whole-genome CRISPR interference screens identify ARID1A-dependent growth regulators in human induced pluripotent stem cells.

Perturbing expression is a powerful way to understand the role of individual genes, but can be challenging in important models. CRISPR-Cas screens in human induced pluripotent stem cells (iPSCs) are of limited efficiency due to DNA break-induced stress, while the less stressful silencing with an inactive Cas9 has been considered less effective so far. Here, we developed the dCas9-KRAB-MeCP2 fusion protein for screening in iPSCs from multiple donors.

Rule-Governed Behavior: Teaching Social Skills via Rule-Following to Children with Autism.

Rule-governed behavior (RGB) is behavior that is controlled by verbal descriptions of contingencies rather than by direct contact or a history of direct contact with the contingencies. Humans rely on RGB to navigate a multitude of life experiences, and in doing so, we avoid direct contact with destructive or harmful contingencies or contingencies that would be inefficient to contact. However, individuals with autism spectrum disorders (ASDs) frequently struggle with RGB, leaving them at increased risk of contacting aversive consequences.