Cell Adhesion: A surprising cohesive force

When an experimentalist or a biological mechanism applies an external force onto a cell chemically sticking to its substrate, a reacting "suction" force, due to the slow penetration of the surrounding fluid between the cell and the substrate, opposes to the dissociation. This force can overcome other known adhesive forces when the process is sufficiently violent (typically 10^5^ pN). Its maximal contribution to the total adhesive energy of the cell can then be estimated to 2 10^-3^ J/m2. The physical origin of this effect is quite simple, and it may be compared with that leaning a "suction-cup" against a bathroom wall. We address the consequences of this effect on (i) the separation energy, (ii) the motion of the fluid surrounding the cell, more especially, on the pumping of the fluid by moving cells, and (iii) the inhibition of cell motion

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015

142P Correlating total tumor volume on CT-Scan and liquid biopsy ctDNA in 1017 patients with metastatic cancer: A novel study

International audienceLiquid biopsy is an emerging technology capable of detecting cancer, while CT-imaging is the gold standard. We aim to correlate imaging features from CT-scans to liquid biopsy ctDNA tumor fraction (TF) and blood Tumor Mutational Burden (bTMB)