A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p

Search for new phenomena in events with same-charge leptons and b-jets in pp collisions at √s=13 TeV with the ATLAS detector

A search for new phenomena in events with two same-charge leptons or three leptons and jets identified as originating from $b$-quarks in a data sample of 36.1 fb$^{-1}$ of $pp$ collisions at $\sqrt{s}= 13$ TeV recorded by the ATLAS detector at the Large Hadron Collider is reported. No significant excess is found and limits are set on vector-like quark, four-top-quark, and same-sign top-quark pair production. The observed (expected) 95% CL mass limits for a vector-like $T$- and $B$-quark singlet are $m_T > 0.98$ $(0.99)$ TeV and $m_B > 1.00$ $(1.01)$ TeV respectively. Limits on the production of the vector-like $T_{5/3}$-quark are also derived considering both pair and single production; in the former case the lower limit on the mass of the $T_{5/3}$-quark is (expected to be) 1.19 (1.21) TeV. The Standard Model four-top-quark production cross-section upper limit is (expected to be) 69 (29) fb. Constraints are also set on exotic four-top-quark production models. Finally, limits are set on same-sign top-quark pair production. The upper limit on $uu \to tt$ production is (expected to be) 89 (59) fb for a mediator mass of 1 TeV, and a dark-matter interpretation is also derived, excluding a mediator of 3 TeV with a dark-sector coupling of 1.0 and a coupling to ordinary matter above 0.31