Mammalian Brain As a Network of Networks

Acknowledgements AZ, SG and AL acknowledge support from the Russian Science Foundation (16-12-00077). Authors thank T. Kuznetsova for Fig. 6.Peer reviewedPublisher PD

The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level

A multidimensional perspective on microbial interactions

Beyond being simply positive or negative, beneficial or inhibitory, microbial interactions can involve a diverse set of mechanisms, dependencies and dynamical properties. These more nuanced features have been described in great detail for some specific types of interactions, (e.g. pairwise metabolic cross-feeding, quorum sensing or antibiotic killing), often with the use of quantitative measurements and insight derived from modeling. With a growing understanding of the composition and dynamics of complex microbial communities for human health and other applications, we face the challenge of integrating information about these different interactions into comprehensive quantitative frameworks. Here, we review the literature on a wide set of microbial interactions, and explore the potential value of a formal categorization based on multidimensional vectors of attributes. We propose that such an encoding can facilitate systematic, direct comparisons of interaction mechanisms and dependencies, and we discuss the relevance of an atlas of interactions for future modeling and rational design efforts.R01 GM121950 - NIGMS NIH HHSPublished versio

A Similarity Based Approach for Chemical Category Classification

This report aims to describe the main outcomes of an IHCP Exploratory Research Project carried out during 2005 by the European Chemicals Bureau (Computational Toxicology Action). The original aim of this project was to develop a computational method to facilitate the classification of chemicals into similarity-based chemical categories, which would be both useful for building (Q)SAR models (research application) and for defining chemical category proposals (regulatory application).JRC.I-Institute for Health and Consumer Protection (Ispra

Leveraging Citation Networks to Visualize Scholarly Influence Over Time

Assessing the influence of a scholar's work is an important task for funding organizations, academic departments, and researchers. Common methods, such as measures of citation counts, can ignore much of the nuance and multidimensionality of scholarly influence. We present an approach for generating dynamic visualizations of scholars' careers. This approach uses an animated node-link diagram showing the citation network accumulated around the researcher over the course of the career in concert with key indicators, highlighting influence both within and across fields. We developed our design in collaboration with one funding organization---the Pew Biomedical Scholars program---but the methods are generalizable to visualizations of scholarly influence. We applied the design method to the Microsoft Academic Graph, which includes more than 120 million publications. We validate our abstractions throughout the process through collaboration with the Pew Biomedical Scholars program officers and summative evaluations with their scholars

Regulation of tomato fruit ripening

Fruit ripening is a sophisticatedly orchestrated developmental process, unique to plants, that results in major physiological and metabolic changes, ultimately leading to fruit decay and seed dispersal. Because of their strong impact on fruit nutritional and sensory qualities, the ripeningassociated changes have been a matter of sustained investigation aiming at unravelling the molecular and genetic basis of fruit ripening. Tomato rapidly emerged as the model of choice for fleshy fruit research and a wealth of genetic resources and genomics tools have been developed, providing new entries into the regulatory mechanisms involved in the triggering and coordination of the ripening process. Some of the key components participating in the control of tomato fruit ripening have been uncovered, but our knowledge of the network of signalling pathways engaged in this complex developmental process remains fragmentary. This review highlights the main advances and emphasizes issues still to be addressed using the rapidly developing ‘omics’ approaches