Food web topology and nested keystone species complexes

Important species may be in critically central network positions in ecological interaction networks. Beyond quantifying which one is the most central species in a food web, a multi-node approach can identify the key sets of the most central n species as well. However, for sets of different size n, these structural keystone species complexes may differ in their composition. If larger sets contain smaller sets, higher nestedness may be a proxy for predictive ecology and efficient management of ecosystems. On the contrary, lower nestedness makes the identification of keystones more complicated. Our question here is how the topology of a network can influence nestedness as an architectural constraint. Here, we study the role of keystone species complexes in 27 real food webs and quantify their nestedness. After quantifying their topology properties, we determine their keystones species complexes, calculate their nestedness and statistically analyze the relationship between topological indices and nestedness. A better understanding of the cores of ecosystems is crucial for efficient conservation efforts and to know which networks will have more nested keystone species complexes would be a great help for prioritizing species that could preserve the ecosystem’s structural integrity

Molecular dynamics recipes for genome research

Molecular dynamics (MD) simulation allows one to predict the time evolution of a system of interacting particles. It is widely used in physics, chemistry and biology to address specific questions about the structural properties and dynamical mechanisms of model systems. MD earned a great success in genome research, as it proved to be beneficial in sorting pathogenic from neutral genomic mutations. Considering their computational requirements, simulations are commonly performed on HPC computing devices, which are generally expensive and hard to administer. However, variables like the software tool used for modeling and simulation or the size of the molecule under investigation might make one hardware type or configuration more advantageous than another or even make the commodity hardware definitely suitable for MD studies. This work aims to shed lights on this aspect

Food Web Topology and Nested Keystone Species Complexes

Important species may be in critically central network positions in ecological interaction networks. Beyond quantifying which one is the most central species in a food web, a multi-node approach can identify the key sets of the most central n species as well. However, for sets of different size n, these structural keystone species complexes may differ in their composition. If larger sets contain smaller sets, higher nestedness may be a proxy for predictive ecology and efficient management of ecosystems. On the contrary, lower nestedness makes the identification of keystones more complicated. Our question here is how the topology of a network can influence nestedness as an architectural constraint. Here, we study the role of keystone species complexes in 27 real food webs and quantify their nestedness. After quantifying their topology properties, we determine their keystones species complexes, calculate their nestedness and statistically analyze the relationship between topological indices and nestedness. A better understanding of the cores of ecosystems is crucial for efficient conservation efforts and to know which networks will have more nested keystone species complexes would be a great help for prioritizing species that could preserve the ecosystem’s structural integrity

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis

MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater’s papilla adenocarcinoma

iRNA expression abnormalities in adenocarcinoma arising from pancreatic ductal system (PDAC) and Vater’s papilla (PVAC) could be associated with distinctive pathologic features and clinical cancer behaviours. Our previous miRNA expression profiling data on PDAC (n=9) and PVAC (n=4) were revaluated to define differences/ similarities in miRNA expression patterns. Afterwards, in order to uncover target genes and core signalling pathways regulated by specific miRNAs in these two tumour entities, miRNA interaction networks were wired for each tumour entity, and experimentally validated target genes underwent pathways enrichment analysis. One hundred and one miRNAs were altered, mainly over-expressed, in PDAC samples. Twenty-six miRNAs were deregulated in PVAC samples, where more miRNAs were down-expressed in tumours compared to normal tissues. Four miRNAs were significantly altered in both subgroups of patients, while 27 miRNAs were differentially expressed between PDAC and PVAC. Although miRNA interaction networks were more complex and dense in PDAC than in PVAC, pathways enrichment analysis uncovered a functional overlapping between PDAC and PVAC. However, shared signalling events were influenced by different miRNA and/or genes in the two tumour entities. Overall, specific miRNA expression patterns were involved in the regulation of a limited core signalling pathways in the biology landscape of PDAC and PVAC

The Complex Story Behind a Deep Eutectic Solvent Formation as Revealed by L‑Menthol Mixtures with Butylated Hydroxytoluene Derivatives.

An in-depth study of the hydrophobic eutectic mixtures formed by L-menthol (MEN) with the butylated hydroxytoluene (BHT), 2-tert-butyl-pcresol (TBC), and p-cresol (PC) compounds has been carried out, where TBC and PC are analogous to the BHT species but with a different degree of steric hindrance around the hydroxyl group. Thermal characterization evidenced that the BHT/MEN system can be classified as an ideal eutectic, while the TBC/MEN and PC/MEN mixtures behave as type V deep eutectic solvents (DESs) for a wide range of compositions around the eutectic point. As shown by an array of experimental and theoretical methods, in the BHT/MEN mixtures the establishment of hydrogen-bond (H-bond) interactions between the components is dramatically hampered because of the steric hindrance in the BHT molecule, so that the achievement of a liquid phase at room temperature for the eutectic composition is driven by apolar−apolar attractions among the alkyl functional groups of the constituents. Differently, the TBC-MEN donor−receptor H-bond is the main driving force for the formation of a type V DES and derives from a concurrence of electronic and steric factors characterizing the TBC molecule. Finally, the absence of steric hindrance around the hydroxyl group allows the self-association among PC molecules through H-bonded networks already in the pristine compound, but the replacement with the more favorable PC-MEN H-bond provides a type V DES upon mixing of these components. Our combined approach, together with the peculiarity of the inspected systems, delivered an archetypal study able to shed light onto the various contributions ruling the structure− properties relationship in DESs and possibly deepening the currently accepted view of these inherently complex media

Systematic Analysis of Mouse Genome Reveals Distinct Evolutionary and Functional Properties Among Circadian and Ultradian Genes

In living organisms, biological clocks regulate 24 h (circadian) molecular, physiological, and behavioral rhythms to maintain homeostasis and synchrony with predictable environmental changes, in particular with those induced by Earth's rotation on its axis. Harmonics of these circadian rhythms having periods of 8 and 12 h (ultradian) have been documented in several species. In mouse liver, harmonics of the 24-h period of gene transcription hallmarked genes oscillating with a frequency two or three times faster than circadian periodicity. Many of these harmonic transcripts enriched pathways regulating responses to environmental stress and coinciding preferentially with subjective dawn and dusk. At this time, the evolutionary history of genes with rhythmic expression is still poorly known and the role of length-of-day changes due to Earth's rotation speed decrease over the last four billion years is totally ignored. We hypothesized that ultradian and stress anticipatory genes would be more evolutionarily conserved than circadian genes and background non-oscillating genes. To investigate this issue, we performed broad computational analyses of genes/proteins oscillating at different frequency ranges across several species and showed that ultradian genes/proteins, especially those oscillating with a 12-h periodicity, are more likely to be of ancient origin and essential in mice. In summary, our results show that genes with ultradian transcriptional patterns are more likely to be phylogenetically conserved and associated with the primeval and inevitable dawn/dusk transitions

Reverse engineering of natural systems by graph theory

With the advent of high-throughput technology, Biological research widened its horizons in terms of biomarkers and mechanisms of action of several diseases and phenotypes. On the other hand, complex diseases, like diabetes, several neurodegenerative pathologies and cancer, are still orphan of a cause and then of a cure. One of the possible reasons is that these are not strictly monogenic diseases since they result from a global interplay between molecular players and master regulators. In this context, where “the whole is something over and above its parts and not just the sum of them all” (Aristotle 384-322 B.C.), is clear that the Cartesian reductionism cannot completely help understand how a disease arises and develops. Systems Biology comes on the stage here and puts emphasis on whole behavior as being basically indivisible. It sustains the Smuts’s holistic theory according to which whole systems such as cells, tissues, organisms, and populations were proposed to have unique emergent properties and that it was impossible to reassemble the behavior of the whole from the properties of the individual components. Hence, new technologies were necessary to define and understand the behavior of systems. New mathematical models and computational approaches emerged in the past decades. Thereby taking inspiration from the theory of graphs. Aspects of nature that could be explained by the interaction of individual agents were modeled as networks and their properties studied topologically. Speculations on the global structure of biological systems were based on two important assertions: systems have a hierarchical structure, and the structure is held together by numerous linkages to construct very complex networks. In this work, we retrace this path by first reconstructing and studying a complex molecular system made by gene and microRNA expression profiles in patients affected by colorectal cancer. We show how the study of topological properties of the system helped identifying a tiny subnetwork of master-regulator and effectors that, individually, were associated to poor survival rates when extremely expressed. Group-effects were not captured, until the development of Pyntacle, a cross-platform and open source Python suite of high-performance computing algorithms for the discovery of key-players in networks. Pyntacle is introduced and presented in this work and then used proficiently in two other case studies. The former regards ecological food webs and reports on the assessment of their nestedness property, which is an indicator of their global robustness and redundancy. The latter is an exploration of the relationships between sex and ageing process in Drosophila melanogaster, which developed into two computational steps: definition of co-expressing modules of genes and identification of sex independent key-players molecules in male and female flies