Classification of triple negative breast cancer by epithelial mesenchymal transition and the tumor immune microenvironment.

Triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancers and differs from other invasive breast cancer types because it grows and spreads rapidly, it has limited treatment options and typically worse prognosis. Since TNBC does not express estrogen or progesterone receptors and little or no human epidermal growth factor receptor (HER2) proteins are present, hormone therapy and drugs targeting HER2 are not helpful, leaving chemotherapy only as the main systemic treatment option. In this context, it would be important to find molecular signatures able to stratify patients into high and low risk groups.

Predicting the failure of two-dimensional silica glasses.

Being able to predict the failure of materials based on structural information is a fundamental issue with enormous practical and industrial relevance for the monitoring of devices and components. Thanks to recent advances in deep learning, accurate failure predictions are becoming possible even for strongly disordered solids, but the sheer number of parameters used in the process renders a physical interpretation of the results impossible. Here we address this issue and use machine learning methods to predict the failure of simulated two dimensional silica glasses from their initial undeformed structure.

Information Optimized Multilayer Network Representation of High Density Electroencephalogram Recordings.

High-density electroencephalography (hd-EEG) provides an accessible indirect method to record spatio-temporal brain activity with potential for disease diagnosis and monitoring. Due to their highly multidimensional nature, extracting useful information from hd-EEG recordings is a complex task. Network representations have been shown to provide an intuitive picture of the spatial connectivity underlying an electroencephalogram recording, although some information is lost in the projection.

Classification of triple-negative breast cancers through a Boolean network model of the epithelial-mesenchymal transition.

Predicting the metastasis risk in patients with a primary breast cancer tumor is of fundamental importance to decide the best therapeutic strategy in the framework of personalized medicine. Here, we present ARIADNE, a general algorithmic strategy to assess the risk of metastasis from transcriptomic data of patients with triple-negative breast cancer, a subtype of breast cancer with poorer prognosis with respect to the other subtypes. ARIADNE identifies hybrid epithelial/mesenchymal phenotypes by mapping gene expression data into the states of a Boolean network model of the epithelial-mesenchymal pathway.

A Standardized Project Gutenberg Corpus for Statistical Analysis of Natural Language and Quantitative Linguistics.

The use of Project Gutenberg (PG) as a text corpus has been extremely popular in statistical analysis of language for more than 25 years. However, in contrast to other major linguistic datasets of similar importance, no consensual full version of PG exists to date. In fact, most PG studies so far either consider only a small number of manually selected books, leading to potential biased subsets, or employ vastly different pre-processing strategies (often specified in insufficient details), raising concerns regarding the reproducibility of published results.

Automatic design of mechanical metamaterial actuators.

Mechanical metamaterial actuators achieve pre-determined input-output operations exploiting architectural features encoded within a single 3D printed element, thus removing the need for assembling different structural components. Despite the rapid progress in the field, there is still a need for efficient strategies to optimize metamaterial design for a variety of functions. We present a computational method for the automatic design of mechanical metamaterial actuators that combines a reinforced Monte Carlo method with discrete element simulations.

MicroRNA-222 Regulates Melanoma Plasticity.

Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood.

Comparative analysis of metabolic and transcriptomic features of .

Some species have a longer lifespan than others, but usually lifespan is correlated with typical body weight. Here, we study the lifetime evolution of the metabolic behaviour of , a killifish with an extremely short lifespan with respect to other fishes, even when taking into account rescaling by body weight. Comparison of the gene expression patterns of with those of zebrafish and mouse () shows that a broad set of metabolic genes and pathways are affected in during ageing in a way that is consistent with a global deregulation of chromatin.

Author Correction: Identifying inhibitors of epithelial-mesenchymal plasticity using a network topology-based approach.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Identifying inhibitors of epithelial-mesenchymal plasticity using a network topology-based approach.

Metastasis is the cause of over 90% of cancer-related deaths. Cancer cells undergoing metastasis can switch dynamically between different phenotypes, enabling them to adapt to harsh challenges, such as overcoming anoikis and evading immune response. This ability, known as phenotypic plasticity, is crucial for the survival of cancer cells during metastasis, as well as acquiring therapy resistance.

Blood Flow Contributions to Cancer Metastasis.

The distribution patterns of cancer metastasis depend on a sequence of steps involving adhesion molecules and on mechanical and geometrical effects related to blood circulation, but how much each of these two aspects contributes to the metastatic spread of a specific tumor is still unknown. Here we address this question by simulating cancer cell trajectories in a high-resolution humanoid model of global blood circulation, including stochastic adhesion events, and comparing the results with the location of metastasis recorded in thousands of human autopsies for seven different solid tumors, including lung, prostate, pancreatic and colorectal cancers, showing that on average 40% of the variation in the metastatic distribution can be attributed to blood circulation. Our humanoid model of circulating tumor cells allows us to predict the metastatic spread in specific realistic conditions and can therefore guide precise therapeutic interventions to fight metastasis.

Chromatin and Cytoskeletal Tethering Determine Nuclear Morphology in Progerin-Expressing Cells.

The nuclear morphology of eukaryotic cells is determined by the interplay between the lamina forming the nuclear skeleton, the chromatin inside the nucleus, and the coupling with the cytoskeleton. Nuclear alterations are often associated with pathological conditions as in Hutchinson-Gilford progeria syndrome, in which a mutation in the lamin A gene yields an altered form of the protein, named progerin, and an aberrant nuclear shape. Here, we introduce an inducible cellular model of Hutchinson-Gilford progeria syndrome in HeLa cells in which increased progerin expression leads to alterations in the coupling of the lamin shell with cytoskeletal or chromatin tethers as well as with polycomb group proteins.

Author Correction: Probing spermiogenesis: a digital strategy for mouse acrosome classification.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Phase transition, scaling of moments, and order-parameter distributions in Brownian particles and branching processes with finite-size effects.

We revisit the problem of Brownian diffusion with drift in order to study finite-size effects in the geometric Galton-Watson branching process. This is possible because of an exact mapping between one-dimensional random walks and geometric branching processes, known as the Harris walk. In this way, first-passage times of Brownian particles are equivalent to sizes of trees in the branching process (up to a factor of proportionality).

Topography of epithelial-mesenchymal plasticity.

The transition between epithelial and mesenchymal states has fundamental importance for embryonic development, stem cell reprogramming, and cancer progression. Here, we construct a topographic map underlying epithelial-mesenchymal transitions using a combination of numerical simulations of a Boolean network model and the analysis of bulk and single-cell gene expression data. The map reveals a multitude of metastable hybrid phenotypic states, separating stable epithelial and mesenchymal states, and is reminiscent of the free energy measured in glassy materials and disordered solids.

Gene expression signature of obesity in monozygotic twins.

Objective: Observational studies suggest that obesity might have a Mendelian origin, but it is not clear if gene expression patterns observed in obese subjects are secondary to genetic traits or not.

Approach: Here we test a transcriptomic signature of obesity previously identified by our group on a large cohort of twin subjects (TwinsUK).

Main Results: The results show that the signature correlates strongly both with body mass index (BMI) and fat mass.

Dependence of exponents on text length versus finite-size scaling for word-frequency distributions.

Some authors have recently argued that a finite-size scaling law for the text-length dependence of word-frequency distributions cannot be conceptually valid. Here we give solid quantitative evidence for the validity of this scaling law, using both careful statistical tests and analytical arguments based on the generalized central-limit theorem applied to the moments of the distribution (and obtaining a novel derivation of Heaps' law as a by-product). We also find that the picture of word-frequency distributions with power-law exponents that decrease with text length [X.

Integrative analysis of pathway deregulation in obesity.

Obesity is a pandemic disease, linked to the onset of type 2 diabetes and cancer. Transcriptomic data provides a picture of the alterations in regulatory and metabolic activities associated with obesity, but its interpretation is typically blurred by noise. Here, we solve this problem by collecting publicly available transcriptomic data from adipocytes and removing batch effects using singular value decomposition.

Probing spermiogenesis: a digital strategy for mouse acrosome classification.

Classification of morphological features in biological samples is usually performed by a trained eye but the increasing amount of available digital images calls for semi-automatic classification techniques. Here we explore this possibility in the context of acrosome morphological analysis during spermiogenesis. Our method combines feature extraction from three dimensional reconstruction of confocal images with principal component analysis and machine learning.

Percolation on trees as a Brownian excursion: From Gaussian to Kolmogorov-Smirnov to exponential statistics.

We calculate the distribution of the size of the percolating cluster on a tree in the subcritical, critical, and supercritical phase. We do this by exploiting a mapping between continuum trees and Brownian excursions, and arrive at a diffusion equation with suitable boundary conditions. The exact solution to this equation can be conveniently represented as a characteristic function, from which the following distributions are clearly visible: Gaussian (subcritical), Kolmogorov-Smirnov (critical), and exponential (supercritical).

Exact Derivation of a Finite-Size Scaling Law and Corrections to Scaling in the Geometric Galton-Watson Process.

The theory of finite-size scaling explains how the singular behavior of thermodynamic quantities in the critical point of a phase transition emerges when the size of the system becomes infinite. Usually, this theory is presented in a phenomenological way. Here, we exactly demonstrate the existence of a finite-size scaling law for the Galton-Watson branching processes when the number of offsprings of each individual follows either a geometric distribution or a generalized geometric distribution.

Large-Scale Analysis of Zipf's Law in English Texts.

Despite being a paradigm of quantitative linguistics, Zipf's law for words suffers from three main problems: its formulation is ambiguous, its validity has not been tested rigorously from a statistical point of view, and it has not been confronted to a representatively large number of texts. So, we can summarize the current support of Zipf's law in texts as anecdotic. We try to solve these issues by studying three different versions of Zipf's law and fitting them to all available English texts in the Project Gutenberg database (consisting of more than 30 000 texts).

Mapping high-growth phenotypes in the flux space of microbial metabolism.

Experimental and empirical observations on cell metabolism cannot be understood as a whole without their integration into a consistent systematic framework. However, the characterization of metabolic flux phenotypes is typically reduced to the study of a single optimal state, such as maximum biomass yield that is by far the most common assumption. Here, we confront optimal growth solutions to the whole set of feasible flux phenotypes (FFPs), which provides a benchmark to assess the likelihood of optimal and high-growth states and their agreement with experimental results.

Log-Log Convexity of Type-Token Growth in Zipf's Systems.

It is traditionally assumed that Zipf's law implies the power-law growth of the number of different elements with the total number of elements in a system-the so-called Heaps' law. We show that a careful definition of Zipf's law leads to the violation of Heaps' law in random systems, with growth curves that have a convex shape in log-log scale. These curves fulfill universal data collapse that only depends on the value of Zipf's exponent.

Finite-size scaling of survival probability in branching processes.

Branching processes pervade many models in statistical physics. We investigate the survival probability of a Galton-Watson branching process after a finite number of generations. We derive analytically the existence of finite-size scaling for the survival probability as a function of the control parameter and the maximum number of generations, obtaining the critical exponents as well as the exact scaling function, which is G(y)=2ye(y)/(e(y)-1), with y the rescaled distance to the critical point.