Detection of gene annotations and protein-protein interaction associated disorders through transitive relationships between integrated annotations

Background Gene function annotations, which are associations between a gene and a term of a controlled vocabulary describing gene functional features, are of paramount importance in modern biology. Datasets of these annotations, such as the ones provided by the Gene Ontology Consortium, are used to design novel biological experiments and interpret their results. Despite their importance, these sources of information have some known issues. They are incomplete, since biological knowledge is far from being definitive and it rapidly evolves, and some erroneous annotations may be present. Since the curation process of novel annotations is a costly procedure, both in economical and time terms, computational tools that can reliably predict likely annotations, and thus quicken the discovery of new gene annotations, are very useful. Methods We used a set of computational algorithms and weighting schemes to infer novel gene annotations from a set of known ones. We used the latent semantic analysis approach, implementing two popular algorithms (Latent Semantic Indexing and Probabilistic Latent Semantic Analysis) and propose a novel method, the Semantic IMproved Latent Semantic Analysis, which adds a clustering step on the set of considered genes. Furthermore, we propose the improvement of these algorithms by weighting the annotations in the input set. Results We tested our methods and their weighted variants on the Gene Ontology annotation sets of three model organism genes (Bos taurus, Danio rerio and Drosophila melanogaster ). The methods showed their ability in predicting novel gene annotations and the weighting procedures demonstrated to lead to a valuable improvement, although the obtained results vary according to the dimension of the input annotation set and the considered algorithm. Conclusions Out of the three considered methods, the Semantic IMproved Latent Semantic Analysis is the one that provides better results. In particular, when coupled with a proper weighting policy, it is able to predict a significant number of novel annotations, demonstrating to actually be a helpful tool in supporting scientists in the curation process of gene functional annotations

SOILS EVOLUTION AND TREELINE FLUCTUATIONS ON THE SOUTHERN SIDE OF THE ALPS UNDER HOLOCENE CLIMATE CHANGE

The climate in the Alps has been characterized, from the late 19th century until now, by an increase of the mean annual temperatures by about 2\ub0C. It is known that the climate plays an important role in the ecosystems, particularly in the Alps, where meteorological factors, combined with severe morphological conditions, often show extreme behaviours. The climate is a principal factor governing the natural environment of mountains on short-time scales, and it characterizes the location and the intensity of biological, physical and chemical processes. Since mountains environments are susceptible to the impacts of a rapidly changing climate, they provide interesting locations for the early detection and the study of the signals of climate change and its impacts on the environmental systems. Indeed, in mountain landscapes, biological and abiological responses to variations in climatic conditions are particularly noticeable. The main evidences concern the glacier shrinkage, characterized by a general reduction of glaciers, by a widening of proglacial areas followed by colonization of the vegetation, by the upward shift of the vegetation belts and, in particular, of the treeline. Although altitudinal treelines are widely recognized as climatic boundaries, geomorphological processes and human activities can locally limit the treeline position, conditioning its altitude and dynamics. In fact, in mountain regions, trees establishment and growth at the highest altitudes may be greatly affected by geomorphological processes and/or local human impacts. The aim of this PhD Project is the characterization of the maximum altitude of the treeline for the central part of the Italian Alps, the spatial and statistical investigations of the role of geomorphological processes and related landforms on the treeline position and, finally, the reconstruction of late Holocene soil evolution and environmental changes at the treeline in some sample areas. In order to cover the central and the western part of the Italian Alps and also the northern part of Apennines, five different sample areas were selected: two in the Upper Valtellina (Mt. Confinale and proglacial area of Forni glacier), two in Aosta Valley (Becca di Viou and Saint Nicolas) and one in the Northern Apennines (Mt. Cusna). In order to perform a more complete reconstruction of the environmental changes at the treeline a multidisciplinary approach was used. First, a detailed mapping of the treeline and the determination of the main factors (i. e., geomorphological constraints, climate and human impact) that limit the maximum altitude of the treeline by means of GIS software was performed to reconstruct the treeline position and to choose the sample areas. Survey and sampling of soils was carried out in the sample areas, with the purpose of outlining the general characteristics of the soils and of searching for paleosols and other potential proxy archives. The analysis of the identified soil profiles took advantage of multiple laboratory and microscope techniques to provide both maximum accuracy of data and a wider overview of the aspects involved, with also new methods of analysis like the Rock-Eval pyrolysis and the stable carbon and nitrogen isotopes composition. In addition, a detailed reconstruction of the treeline altitudinal dynamics using a dendrochronological approach and an analysis of climate-growth response using a dendroclimatic approach were performed. Whereas, in the sample areas with high geomorphological influence, the soil erosion rates was investigated using a dendrogeomorphological approach, sampling trees and related exposed roots. From this multidisciplinary approach, the following results are emerged. The treeline elevation in the Upper Valtellina region is primarily limited (82% of trees) by geomorphological constraints (treeline mean elevation 2355 m a.s.l.), whereas 15% of the analyzed trees belong to climatic treeline (treeline mean elevation 2530 m a.s.l.) and human impact influences only 3% of the analyzed trees (treeline mean elevation 2335 m a.s.l.). The results also indicate that the current position of treelines is not only lowered by geomorphological constraints in general but, more specifically, can also be differently affected by different groups or types of geomorphological processes. In this study area, gravitational processes affect 87% of the treeline trees, running and/or channelized water affects 8% of trees, and ice affects only 5% of trees. Gravitational processes represent the most destructive processes of the treeline ecotone and tend to reduce the ecotone width, leading to coinciding treeline and timberline. Furthermore, the landforms related to gravitational processes can create considerable obstacles to the treeline upward shift, especially when they merge (e.g., merging talus cones). As far as the site scale is concerned, in Mt. Confinale study area, the reconstruction of the altitudinal dynamics shows that the treeline elevation over time increased from 2505 m a.s.l. (period 1990\u20131999) to 2531 m a.s.l. (period 2000\u20132009) and, finally, to 2545 m a.s.l. (in 2013) with a rates of ongoing treeline upward shift for the period 2000\u20132009, of up to 2.6 m/y. On the Mt. Confinale study site the presence of geomorphological factors may combine with climatic ones to promote an upward shift in the treeline and also may influence the soil evolution, especially if active geomorphological processes are less intense. The soils, although showing a good degree of development, do not reach the characteristics of a typical forest soil. The presence of not particulary developed soil in the treeline ecotone suggests that the colonization of the Pinus cembra, favored by ecologic, microtopographic and microclimatic factors, is followed by the pedogenesis. The latter, in turn, may favor a more active colonization that could lead to a more marked shift to higher altitude of the vegetation belt. In the proglacial area of the Forni glacier, the soil development fit quite well with the chronosequence approach, although not all pedological parameters seem to follow the age-related trend. In fact, even if these soils have a young age, in only 150 years of pedogenesis some transformations could be noticed. For example in the superficial horizons the organic carbon and total nitrogen content increased as well as the values of crystalline iron oxides, while the content of the amorphous iron oxides decreased according to the deglaciation time. For what concerns the Becca di Viou study sites, the literature attests an upward shift of the treeline in the last century; the obtained pedological and the dendroclimatic data seem to stress a changing in treeline ecotone position, following by a possible shift of the timberline and also by a shift of the soil type. The pedological results also highlight that forest, in the past, could reach higher altitude than today. In Saint Nicolas study area the soil analyses results underline the occurrence of colluvial events that influence the vegetation colonization and soil development. Moreover, the results show the great influence of water driven processes on the environmental evolution and also on soil erosion rates, the latter determined by means of trees roots exposure (local average erosion rates: 1.16 cm/year). Instead, at Mt. Cusna study site, the soil analyses underline the presence of different pedogenetic phases: a first, strongly evident, phase leading to the formation of a brown soil under forest vegetation cover, which was interrupted by a colluvial event; a second phase characterized by the presence of a stable forest cover, which favored the formation of a brown soil, also interrupted by a colluvial events; the present day pedogenetic phase, associated to a vegetation change, in particular at higher altitude the presence of shrub as Vaccinium myrtillus, promoting the cryptopodzolization processes. In conclusion, the multidisciplinary study of all examined sites enlightens the following common traits: the geomorphological processes and related landforms are the most important factor influencing the treeline position; in the areas with a climatic constraint (Mt. Confinale, Progracial area of the Forni glacier and Becca di Viou) an upward shift of vegetation belt and of the soil type has been observed; in the areas with geomorphological constraints (Saint Nicolas and Mt. Cusna) the vegetation and soil responses to climate change are masked by the effects of geomorphological processes, but a different response could be noted between Alpine and Apennine study case due to the slope dynamics and the climatic features

Tree rings as ecological indicator of geomorphic activity in geoheritage studies

Mountain areas are characterized by geomorphic processes, especially mass wasting and snow avalanches, which may impact the landscape affecting also the biological component, trees included. If sites colonized by trees are characterized by geomorphic features with a high Global and Scientific Value, including Representativeness of geomorphological processes, Educational Exemplarity, and Integrity, they can be considered geomorphosites. In the framework of assessment of the Scientific Value of geomorphosites, Ecological Support Role is of great importance. Hence, tree rings derived information can be used as indicators to refine the Scientific Value of the sites and also to propose multidisciplinary approaches to understand landscape dynamics. In fact, trees colonizing sites of geomorphological interest are used for detecting past and present events and tree rings may be considered ecological indicators under different points of view. Arboreal vegetation can register growth disturbances in terms of morphological features, at macro- (particular morphologies of trunks) and micro-scale (annual growth rings, stress indicators like compression wood, traumatic resin ducts), becoming a powerful indicator of the geomorphic activity affecting the landscape. In some cases, combined with other techniques like climate data analysis, they may allow refining the often lacunose historical records of geomorphic events impacting different territories. The integrated analysis carried out in the Loana Valley (Sesia Val Grande UNESCO Geopark, Western Italian Alps), considering a selection of geomorphosites affected by mass wasting processes and snow avalanches and located along a touristic trail, allowed to detect which meteorological thresholds favour hydrogeological instability (i.e. overcome of Mean Annual Rainfall of 6\u201310%). Tree rings data coming from the investigated sites provided information on the recurrence of geomorphic activity, allowing filling gaps within the historical archives, by individuating years during which hydrogeological or snow-related events probably occurred and that were missed (i.e. 1986, 1989, 2001, 2007), and adding details on sites for which temporal constraints had not been found before (i.e. Pizzo Stagno Complex System). Finally, investigated sites demonstrated to differently record the history of instability affecting the area and this difference is mirrored in the sites values that are adopted in the framework of geoheritage analysis (Scientific Value, Ecological Support Role and Educational Exemplarity). The proposed multidisciplinary approach, including geomorphology, dendrogeomorphology and climatology, represents, hence, a useful tool in geoheritage valorisation and management strategies

Clinical Bioinformatics: challenges and opportunities

Background: Network Tools and Applications in Biology (NETTAB) Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics. The NETTAB 2011 workshop, held in Pavia, Italy, in October 2011 was aimed at presenting some of the most relevant methods, tools and infrastructures that are nowadays available for Clinical Bioinformatics (CBI), the research field that deals with clinical applications of bioinformatics. Methods: In this editorial, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions. Results: Some of the most important design features of a CBI-ICT infrastructure are presented, including data warehousing, modularity and flexibility, open-source development, semantic interoperability, integrated search and retrieval of –omics information. Conclusions: Clinical Bioinformatics goals are ambitious. Many factors, including the availability of high-throughput “-omics” technologies and equipment, the widespread availability of clinical data warehouses and the noteworthy increase in data storage and computational power of the most recent ICT systems, justify research and efforts in this domain, which promises to be a crucial leveraging factor for biomedical research

NETTAB 2012 on “Integrated Bio-Search”

The NETTAB 2012 workshop, held in Como on November 14-16, 2012, was devoted to "Integrated Bio-Search", that is to technologies, methods, architectures, systems and applications for searching, retrieving, integrating and analyzing data, information, and knowledge with the aim of answering complex bio-medical-molecular questions, i.e. some of the most challenging issues in bioinformatics today. It brought together about 80 researchers working in the field of Bioinformatics, Computational Biology, Biology, Computer Science and Engineering. More than 50 scientific contributions, including keynote and tutorial talks, oral communications, posters and software demonstrations, were presented at the workshop. This preface provides a brief overview of the workshop and shortly introduces the peer-reviewed manuscripts that were accepted for publication in this Supplement

Alpine gullies system evolution : erosion drivers and control factors. Two examples from the western Italian Alps

Denudation processes affecting mountain slopes may vary according to different factors (e.g., lithology and structural setting of bedrock, climate, relief features), which may be very diverse at the local scale. Gully complex systems, characterised by morphological features similar to those developing in other climate contexts (i.e., pseudo-badlands) are also becoming common at higher altitudes and latitudes. The selected study cases of Gran Gorgia (Susa Valley) and Saint Nicolas (Aosta Valley), in the Western Italian Alps, are sites of geomorphological interest as they are specifically relevant for their scientific features. The aims of this work are (i) reconstructing the morphometric evolution of gully systems and vegetation colonisation time by means of multitemporal spatial analysis on surface morphological changes under water erosion; (ii) reconstructing in detail, through dendrogeomorphological analysis, the progressive spatial surface denudation and changes in erosion rates, by analysing trees and exposed roots and using different indicators (i.e., compression wood, traumatic resin ducts); (iii) obtaining data on successive aggradation/degradation episodes along slopes surrounding such hotspots through geopedological investigations; and (iv) identifying which control factors exert a predominant role on denudation patterns in such contexts. Multidisciplinary analyses regarding the study sites allowed for detailing of erosional history of the studied slopes detecting the prevailing drivers of their evolution. According to the results and considering the common climate and bedrock conditions, the structural background seems to have more influence on slope evolution at the Saint Nicolas site, while superficial geomorphic processes seem to be more relevant at the Gran Gorgia site. Because the sites have already been recognised as part of geoheritage by local authorities, the data obtained in the present research on their genesis, evolution, and local drivers affecting the rates of denudation (i.e., scientific relevance of the site) suggests that description of the sites for dissemination purposes should include links to the entire slope history

Implementing a transcription factor interaction prediction system using the genometric query language

Novel technologies and growing interest have resulted in a large increase in the amount of data available for genomics and transcriptomics studies, both in terms of volume and contents. Biology is relying more and more on computational methods to process, investigate, and extract knowledge from this huge amount of data. In this work, we present the TICA web server (available at http://www.gmql.eu/tica/), a fast and compact tool developed to support data-driven knowledge discovery in the realm of transcription factor interaction prediction. TICA leverages both the GenoMetric Query Language, a novel query tool (based on the Apache Hadoop and Spark technologies) specialized in the integration and management of heterogeneous, large genomic datasets, and a statistical method for robust detection of co-locations across interval-based data, in order to infer physically interacting transcription factors. Notably, TICA allows investigators to upload and analyze their own ChIP-seq experiments datasets, comparing them both against ENCODE data or between themselves, achieving computation time which increases linearly with respect to dataset size and density. Using ENCODE data from three well-studied cell lines as reference, we show that TICA predictions are supported by existing biological knowledge, making the web server a reliable and efficient tool for interaction screening and data-driven hypothesis generation

GenoMetric Query Language: A novel approach to large-scale genomic data management

Motivation: Improvement of sequencing technologies and data processing pipelines is rapidly providing sequencing data, with associated high-level features, of many individual genomes in multiple biological and clinical conditions. They allow for data-driven genomic, transcriptomic and epigenomic characterizations, but require state-of-the-art ‘big data’ computing strategies, with abstraction levels beyond available tool capabilities. Results: We propose a high-level, declarative GenoMetric Query Language (GMQL) and a toolkit for its use. GMQL operates downstream of raw data preprocessing pipelines and supports queries over thousands of heterogeneous datasets and samples; as such it is key to genomic ‘big data’ analysis. GMQL leverages a simple data model that provides both abstractions of genomic region data and associated experimental, biological and clinical metadata and interoperability between many data formats. Based on Hadoop framework and Apache Pig platform, GMQL ensures high scalability, expressivity, flexibility and simplicity of use, as demonstrated by several biological query examples on ENCODE and TCGA datasets. Availability and implementation: The GMQL toolkit is freely available for non-commercial use at http://www.bioinformatics.deib.polimi.it/GMQL/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online