Predicting protein function with hierarchical phylogenetic profiles: The Gene3D phylo-tuner method applied to eukaryotic Genomes

"Phylogenetic profiling'' is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence-absence profiles of orthologous genes is now a common and powerful way of identifying functionally associated genes. In this approach, correctly determining orthology, as a means of identifying functional equivalence between two genes, is a critical and nontrivial step and largely explains why previous work in this area has mainly focused on using presence-absence profiles in prokaryotic species. Here, we demonstrate that eukaryotic genomes have a high proportion of multigene families whose phylogenetic profile distributions are poor in presence-absence information content. This feature makes them prone to orthology mis-assignment and unsuited to standard profile-based prediction methods. Using CATH structural domain assignments from the Gene3D database for 13 complete eukaryotic genomes, we have developed a novel modification of the phylogenetic profiling method that uses genome copy number of each domain superfamily to predict functional relationships. In our approach, superfamilies are subclustered at ten levels of sequence identity from 30% to 100% - and phylogenetic profiles built at each level. All the profiles are compared using normalised Euclidean distances to identify those with correlated changes in their domain copy number. We demonstrate that two protein families will "auto-tune'' with strong co-evolutionary signals when their profiles are compared at the similarity levels that capture their functional relationship. Our method finds functional relationships that are not detectable by the conventional presence - absence profile comparisons, and it does not require a priori any fixed criteria to define orthologous genes

Combining terrestrial stereophotogrammetry, DGPS and GIS-based 3D voxel modelling in the volumetric recording of archaeological features

Archaeological recording of structures and excavations in high mountain areas is greatly hindered by the scarce availability of both space, to transport material, and time. The Madriu-Perafita-Claror, InterAmbAr and PCR Mont Lozère high mountain projects have documented hundreds of archaeological structures and carried out many archaeological excavations. These projects required the development of a technique which could record both structures and the process of an archaeological excavation in a fast and reliable manner.The combination of DGPS, close-range terrestrial stereophotogrammetry and voxel based GIS modelling offered a perfect solution since it helped in developing a strategy which would obtain all the required data on-site fast and with a high degree of precision. These data are treated off-site to obtain georeferenced orthoimages covering both the structures and the excavation process from which site and excavation plans can be created. The proposed workflow outputs also include digital surface models and volumetric models of the excavated areas from which topography and archaeological profiles were obtained by voxel-based GIS procedures. In this way, all the graphic recording required by standard archaeological practices was met. © 2012 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS)

Assessing functional novelty of PSI structures via structure-function analysis of large and diverse superfamilies

The structural genomics initiatives have had as one of their aims to improve our understanding of protein function by providing representative structures for many structurally uncharacterised protein families. As suggested by the recent assessment of the Protein Structure Initiative (Structural Genomics Initiative, funded by the NIH), doubts have arisen as to whether Structural Genomics as initially planned were really beneficial to our understanding of biological issues, and in particular of protein function.
A few protein domain superfamilies have been shown to account for unexpectedly large numbers of proteins encoded in fully sequenced genomes. These large superfamilies are generally very diverse, spanning a wide range of functions, both in terms of molecular activities and biological processes. Some of these superfamilies, such as the Rossmann-fold P-loop nucleotide hydrolases or the TIM-barrel glycosidases, have been the subject of extensive structural studies which in turn have shed light on how evolution of the sequence and structure properties produce functional diversity amongst homologues. Recently, the Structure-Function Linkage Database (SFLD) has been setup with the aim of helping the study of structure-function correlations in such superfamilies. Since the evolutionary success of these large superfamilies suggests biological importance, several Structural Genomics Centers have focused on providing full structural coverage for representatives of all sequence families in these superfamilies.
In this work we evaluate structure/function diversity in a set of these large superfamilies and attempt to assess the quality and quantity of biological information gained from Structural Genomics.
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Neural-Based Nonlinear Device Models for Intermodulation Analysis

A new procedure to learn a nonlinear model together with its derivative parameters using a composite neural network is presented.So far neural networks have never been used to extract large-signal device model accounting for distortion parameters.Applying this method to FET devices leads to nonlinear models for current- voltage functions which allow improved prediction of weak and mildly device nonlinearities in the whole bias region. The resulting models have demonstrated to be suitable for both small-signal and large-signal analyses,including intermodulation distortion prediction

Crystal structures of the human Dysferlin inner DysF domain

Background: Mutations in dysferlin, the first protein linked with the cell membrane repair mechanism, causes a group of muscular dystrophies called dysferlinopathies. Dysferlin is a type two-anchored membrane protein, with a single C terminal trans-membrane helix, and most of the protein lying in cytoplasm. Dysferlin contains several C2 domains and two DysF domains which are nested one inside the other. Many pathogenic point mutations fall in the DysF domain region. Results: We describe the crystal structure of the human dysferlin inner DysF domain with a resolution of 1.9 Angstroms. Most of the pathogenic mutations are part of aromatic/arginine stacks that hold the domain in a folded conformation. The high resolution of the structure show that these interactions are a mixture of parallel ring/guanadinium stacking, perpendicular H bond stacking and aliphatic chain packing. Conclusions: The high resolution structure of the Dysferlin DysF domain gives a template on which to interpret in detail the pathogenic mutations that lead to disease

Large-scale, multi-temporal remote sensing of palaeo-river networks: A case study from Northwest India and its implications for the indus civilisation

© 2018 by the authors. Remote sensing has considerable potential to contribute to the identification and reconstruction of lost hydrological systems and networks. Remote sensing-based reconstructions of palaeo-river networks have commonly employed single or limited time-span imagery, which limits their capacity to identify features in complex and varied landscape contexts. This paper presents a seasonal multi-temporal approach to the detection of palaeo-rivers over large areas based on long-term vegetation dynamics and spectral decomposition techniques. Twenty-eight years of Landsat 5 data, a total of 1711 multi-spectral images, have been bulk processed using Google Earth Engine. © Code Editor and cloud computing infrastructure. The use of multi-temporal data has allowed us to overcome seasonal cultivation patterns and long-term visibility issues related to recent crop selection, extensive irrigation and land-use patterns. The application of this approach on the Sutlej-Yamuna interfluve (northwest India), a core area for the Bronze Age Indus Civilisation, has enabled the reconstruction of an unsuspectedly complex palaeo-river network comprising more than 8000 km of palaeo-channels. It has also enabled the definition of the morphology of these relict courses, which provides insights into the environmental conditions in which they operated. These new data will contribute to a better understanding of the settlement distribution and environmental settings in which this, often considered riverine, civilisation operated.ER

Pitch production during the Roman period: an intensive mountain industry for a globalised economy?

The authors’ research project in the Pyrenees mountains has located and excavated Roman kilns for producing pitch from pine resin. Their investigations reveal a whole sustainable industry, integrated into the local environmental cycle, supplying pitch to the Roman network and charcoal as a spin-off to the local iron extractors. The paper makes a strong case for applying combined archaeological and palaeoenvironmental investigations in upland areas, showing mountain industries to have been not so much marginal and pastoral as key players in the economy of the Roman period and beyond it into the seventh century AD

Pattern matching and pattern discovery algorithms for protein topologies

We describe algorithms for pattern matching and pattern learning in TOPS diagrams (formal descriptions of protein topologies). These problems can be reduced to checking for subgraph isomorphism and finding maximal common subgraphs in a restricted class of ordered graphs. We have developed a subgraph isomorphism algorithm for ordered graphs, which performs well on the given set of data. The maximal common subgraph problem then is solved by repeated subgraph extension and checking for isomorphisms. Despite the apparent inefficiency such approach gives an algorithm with time complexity proportional to the number of graphs in the input set and is still practical on the given set of data. As a result we obtain fast methods which can be used for building a database of protein topological motifs, and for the comparison of a given protein of known secondary structure against a motif database

Simulating communication routes in Mediterranean alluvial plains

Societies exchange knowledge, ideas and merchandise throughout their territories. Topography plays a fundamental role in the trajectory of such movements whilst helping to explain the distribution of human constructions. Standard GIS functions have been employed widely to simulate communication routes between settlements, but the straight application of published least cost route models proved inadequate for Mediterranean alluvial plain areas in which seasonal floods become an important factor to acknowledge. The objective of this study is the production of a new model, using topographic and hydrologic factors as variables from which it would be possible to simulate a route, and test it against known Roman itineraries. The selected Roman stretches are Girona – Coll de Pannisars and Tarragona – Montblanc. The new model shows the need to consider each case individually but also stresses the hydrologic factor, expressed in seasonal floods, as being of prime importance in the creation and development of Roman roads in Mediterranean alluvial plains