Classifying pairs with trees for supervised biological network inference

Networks are ubiquitous in biology and computational approaches have been largely investigated for their inference. In particular, supervised machine learning methods can be used to complete a partially known network by integrating various measurements. Two main supervised frameworks have been proposed: the local approach, which trains a separate model for each network node, and the global approach, which trains a single model over pairs of nodes. Here, we systematically investigate, theoretically and empirically, the exploitation of tree-based ensemble methods in the context of these two approaches for biological network inference. We first formalize the problem of network inference as classification of pairs, unifying in the process homogeneous and bipartite graphs and discussing two main sampling schemes. We then present the global and the local approaches, extending the later for the prediction of interactions between two unseen network nodes, and discuss their specializations to tree-based ensemble methods, highlighting their interpretability and drawing links with clustering techniques. Extensive computational experiments are carried out with these methods on various biological networks that clearly highlight that these methods are competitive with existing methods.Comment: 22 page

Unforeseen high temperature and humidity stability of FeCl3_3 intercalated few layer graphene

We present the first systematic study of the stability of the structure and electrical properties of FeCl$_3$ intercalated few-layer graphene to high levels of humidity and high temperature. Complementary experimental techniques such as electrical transport, high resolution transmission electron microscopy and Raman spectroscopy conclusively demonstrate the unforeseen stability of this transparent conductor to a relative humidity up to $100 \%$ at room temperature for 25 days, to a temperature up to 150\,^\circC in atmosphere and up to a temperature as high as 620\,^\circC in vacuum, that is more than twice higher than the temperature at which the intercalation is conducted. The stability of FeCl$_3$ intercalated few-layer graphene together with its unique values of low square resistance and high optical transparency, makes this material an attractive transparent conductor in future flexible electronic applications.Comment: Scientific Reports, volume 5, article no. 760

Aharonov-Bohm effect in graphene

We investigate experimentally transport through ring-shaped devices etched in graphene and observe clear Aharonov-Bohm conductance oscillations. The temperature dependence of the oscillation amplitude indicates that below 1 K the phase coherence length is comparable to or larger than the size of the ring. An increase in the amplitude is observed at high magnetic field, when the cyclotron diameter becomes comparable to the width of the arms of the ring. By measuring the dependence on gate voltage, we also observe an unexpected linear dependence of the oscillation amplitude on the ring conductance, which had not been reported earlier in rings made using conventional metals or semiconducting heterostructures.Comment: 14 pages, 5 figure

Identificación de nuevos componentes del divisoma de Corynebacterineae mediante una estrategia proteómica de marcado por proximidad en las células vivas

La división celular bacteriana es un proceso dirigido por el divisoma, un complejo macromolecular cuyo ensamblaje comienza con la polimerización de la proteína FtsZ en el sitio de división. FtsZ participa en el posterior reclutamiento de otras proteínas del divisoma, que en el caso de Escherichia coli y Bacillus subtilis han sido en identificadas y caracterizadas. Sin embargo, el suborden Corynebacterineae (que incluye importantes patógenos humanos) carece de homólogos reconocibles para muchas de estas proteínas de división celular. Este trabajo se centra en descifrar la arquitectura molecular del divisoma en este grupo de bacterias. Para ello, desarrollamos y optimizamos una estrategia proteómica basada en la biotinilación por proximidad para estudiar el divisoma de Corynebacterium glutamicum. Generamos una cepa que expresa FtsZ fusionada a una ascorbato peroxidasa ingenierizada (APEX2). APEX2 cataliza la oxidación de fenol biotina en presencia de H2O2 dando lugar a un radical que reacciona con aminoácidos de proteínas cercanas. Esto nos permitió marcar el entorno proteómico de FtsZ en la célula viva para su purificación e identificación por Espectrometría de Masa. Obtuvimos así una lista de 159 proteínas, la cual fue filtrada utilizando criterios proteómicos y un exhaustivo análisis bibliográfico para seleccionar candidatos a validar. Se expresaron en C. glutamicum los candidatos fusionados a mNeon para evaluar su localización subcelular. Con esto pudimos identificar 6 proteínas sin función asignada previamente que localizan en el septo, como promitentes nuevos integrantes del divisoma. Futuros estudios permitirán la caracterización de estas proteínas y su rol en la división celular de Corynebacterineae.Agencia Nacinal de Investigación e Innovació

Unraveling corynebacterial divisome composition by proximity labeling in the living cell

Bacterial cell division is directed by the divisome, a protein complex whose assembly begins with the polymerization of FtsZ at midcell to form a ring (Z-ring) This structure participates in the recruitment of other divisome proteins, that in the case of the model bacilli (Escherichia coli and Bacillus subtilis) have been identified and characterized. However, the order Corynebacteriales (that includes important human pathogens as Mycobacterium tuberculosis and Corynebacterium diphtheriae) lacks recognizable homologues for many of these cell division proteins, and the ones fulfilling these missing functions are yet to be identified. To identify the unknown pieces of the corynebacterial divisome, we developed and optimized a proteomic strategy based on proximity biotinylation in the living cell, using Corynebacterium glutamicum as a model organism. We generated a strain expressing FtsZ fused to an engineered ascorbate peroxidase (APEX2). APEX2 catalyzes the oxidation of phenol biotin in the presence of H2O2 giving rise to a radical that reacts with amino acids of nearby proteins. This allowed us to label the proteomic environment of FtsZ in the living cell, and its purification and identification by Mass Spectrometry. We corroborated that APEX2 is active in the biochemical background of C. glutamicum, and optimized the labelling strategy to guarantee the identification of physiologically relevant FtsZ neighbours. We identified a confident list of 253 FtsZ neighbors, that includes known cell division proteins as well as an important number of non-characterized proteins, which represents putative new divisome components. We focused on hypothetical membrane proteins, that might mediate membrane anchor of the Z-ring, as most of the proteins fulfilling this role in E. coli and B. subtilis are not present in corynebacterial genomes. We generate strains expressing the selected candidates fused to a fluorescent proof to evaluate their subcellular localization and their interaction with FtsZ. The results allowed us to identify new conserved membrane bound components of the corynebacterial divisome. Their precise role in cell division, the molecular details of its interaction with the Z-ring and its regulation by protein phosphorylation are being studied.Agencia Nacinal de Investigación e InnovaciónECOS-Sud France-Uruguay U20B0

Desarrollo de una estrategia proteómica basada en el marcado por proximidad in vivo para la identificación de vecinos de la proteína de división celular FtsZ de Corynebacterium glutamicum

La división celular bacteriana es un proceso dirigido por el divisoma, un complejo macromolecular cuyo ensamblaje comienza con la polimerización de la proteína FtsZ en el sitio de división. FtsZ participa en el posterior reclutamiento de otras proteínas componentes del divisoma, que en el caso de Escherichia coli y Bacillus subtilis fueron identificadas y caracterizadas. Sin embargo, el suborden Corynebacterineae (que incluye importantes patógenos humanos) carece de homólogos reconocibles para muchas de estas proteínas de división celular, sugiriendo una composición y arquitectura diferente del divisoma. Este trabajo se centra en el desarrollo de estrategias proteómicas basadas en la biotinilación por proximidad para estudiar el divisoma de Corynebacterium glutamicum. Para ello generamos una cepa que expresa FtsZ unida a una ascorbato peroxidasa ingenierizada (APEX2). APEX2 cataliza la oxidación de fenol biotina en presencia de H2O2 dando lugar a un radical que reacciona con aminoácidos de proteínas cercanas y permite su purificación por afinidad e identificación por espectrometría de masa (MS). La utilidad de esta estrategia depende en forma crítica de diseño experimental y la inclusión de controles adecuados. Evaluamos los niveles de expresión FtsZ-APEX2 y sus efectos sobre la división celular y la composición del proteoma. Además, optimizamos las condiciones del marcado in vivo y de la purificación e identificación de péptidos biotinilados por MS. Esto nos permitió obtener una lista de proteínas en la vecindad de FtsZ, incluyendo su principal interactor reportado, lo que valida la estrategia experimental. Futuros estudios permitirán seleccionar candidatos a validar como nuevos integrantes del divisomaAgencia Nacinal de Investigación e Innovació

Random subwindows and extremely randomized trees for image classification in cell biology

Background: With the improvements in biosensors and high-throughput image acquisition technologies, life science laboratories are able to perform an increasing number of experiments that involve the generation of a large amount of images at different imaging modalities/scales. It stresses the need for computer vision methods that automate image classification tasks. Results: We illustrate the potential of our image classification method in cell biology by evaluating it on four datasets of images related to protein distributions or subcellular localizations, and red-blood cell shapes. Accuracy results are quite good without any specific pre-processing neither domain knowledge incorporation. The method is implemented in Java and available upon request for evaluation and research purpose. Conclusion: Our method is directly applicable to any image classification problems. We foresee the use of this automatic approach as a baseline method and first try on various biological image classification problems

Coping with Environmental Constraints: Geographically Divergent Adaptive Evolution and Germination Plasticity in the Transcontinental \u3cem\u3ePopulus tremuloides\u3c/em\u3e

Societal Impact Statement Syntheses clearly show that global warming is affecting ecosystems and biodiversity around the world. New methods and measures are needed to predict the climate resilience of plant species critical to ecosystem stability, to improve ecological management and to support habitat restoration and human well-being. Widespread keystone species such as aspen are important targets in the study of resilience to future climate conditions because they play a crucial role in maintaining various ecosystem functions and may contain genetic material with untapped adaptive potential. Here, we present a new framework in support of climate-resilient revegetation based on comprehensively understood patterns of genetic variation in aspen. Summary Elucidating species\u27 genetic makeup and seed germination plasticity is essential to inform tree conservation efforts in the face of climate change. Populus tremuloides Michx. (aspen) occurs across diverse landscapes and reaches from Alaska to central Mexico, thus representing an early-successional model for ecological genomics. Within drought-affected regions, aspen shows ploidy changes and/or shifts from sexual to clonal reproduction, and reduced diversity and dieback have already been observed. We genotyped over 1000 individuals, covering aspen\u27s entire range, for approximately 44,000 single-nucleotide polymorphisms (SNPs) to assess large-scale and fine-scale genetic structure, variability in reproductive type (sexual/clonal), polyploidy and genomic regions under selection. We developed and implemented a rapid and reliable analysis pipeline (FastPloidy) to assess the presence of polyploidy. To gain insights into plastic responses, we contrasted seed germination from western US and eastern Canadian natural populations under elevated temperature and water stress. Four major genetic clusters were identified range wide; a preponderance of triploids and clonemates was found within western and southern North American regions, respectively. Genomic regions involving approximately 1000 SNPs under selection were identified with association to temperature and precipitation variation. Under drought stress, western US genotypes exhibited significantly lower germination rates compared with those from eastern North America, a finding that was unrelated to differences in mutation load (ploidy). This study provided new insights into the adaptive evolution of a key indicator tree that provisions crucial ecosystem services across North America, but whose presence is steadily declining within its western distribution. We uncovered untapped adaptive potential across the species\u27 range which can form the basis for climate-resilient revegetation