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2014 Other Open Access OPEN
WP1-CNR-ISTI - Ricostruzione di reti di regolazione genica da dati trascrittomici
Caudai C
Some recently proposed approaches to identify genetic regulatory mechanisms from sequencing experiments are briefly described. Since gene expression is influenced by biologica processes in the cell, and both the processes and the related transcription factors are largely unknown, many attempts have been made to solve this problem by blind source separation techniques. We analyse some of these approaches, each based on a linear data model.

See at: ISTI Repository Open Access | CNR IRIS Restricted | CNR IRIS Restricted


2014 Other Open Access OPEN
Ricostruzione tridimensionale della struttura della cromatina da dati tipo Chromosome Conformation Capture. Nota riservata, progetto InterOmics
Caudai C
This document reports part of the WP1-ISTI unit activity in the framework of the national Flagship Project InterOmics, on the 3D chromatin structure analysis from Hi-C experiments. Compared with other methods presented in the literature, our approach uses a new solution model incorporating sound prior knowledge, and a new reconstruction criterion that does not require an explicit translation of the Hi-C data into Euclidean distances between pairs of genomic loci. This approach also allows us to solve the problem in a multiscale setting, by reconstructing significant fragments separately at high resolution and then putting them together through the same criterion applied to lower-resolution data.

See at: ISTI Repository Open Access | CNR IRIS Restricted | CNR IRIS Restricted


2018 Journal article Open Access OPEN
Culture and horticulture: protecting soil quality in urban gardening
Bretzel F, Caudai C, Tassi E, Rosellini I, Scatena M, Pini R
Urban cultivation for food production is of growing importance. The quality of urban soil can be improved by tillage and the incorporation of organic matter, or can be degraded by chemical treatments. Urban gardeners have a role in this process, through the selection of various cultivation techniques. Our study focuses on an allotment area in the town of Pisa (Italy), which since 1995 has been run as a municipal vegetable garden by the residents. We analysed the soil and compared the data with those collected five years previously, to verify the possible changes in soil properties and fertility. We also interviewed the gardeners regarding their backgrounds, motivations and cultivation practices. We looked for possible changes in the soil quality attributable to the cultivation techniques. We found that the allotment holders influenced the soil quality through the cultivation techniques. Organic carbon, electrical conductivity and the content of copper increased unevenly in relation to the gardeners' cultivation practices. At the same time the study highlights that the urban gardeners were not completely aware of how to protect and enhance the fertility and the quality of urban soil. We believe that town councils should be responsible for providing correct information to the allotment holders and thus prevent the possible misuse of urban soil to grow food, as this can affect everyone's health.Source: SCIENCE OF THE TOTAL ENVIRONMENT, vol. 644, pp. 45-51
DOI: 10.1016/j.scitotenv.2018.06.289
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See at: ISTI Repository Open Access | The Science of The Total Environment Restricted | CNR IRIS Restricted | CNR IRIS Restricted | CNR IRIS Restricted | www.sciencedirect.com Restricted


2020 Journal article Open Access OPEN
A multifunctional alternative lawn where warm-season grass and cold-season flowers coexist
Bretzel F, Gaetani M, Vannucchi F, Caudai C, Grossi N, Magni S, Caturegli L, Volterrani M
Lawns provide green infrastructure and ecosystem services for anthropized areas. They have a strong impact on the environment in terms of inputs (water and fertilizers) and maintenance. The use of warm-season grasses, such as Cynodon dactylon (L.) Pers., provides a cost-effective and sustainable lawn in the dry summers of the Mediterranean. In winter, Bermudagrass is dormant and brown, which instead of being a problem could be an opportunity for biodiversity through the coexistence of flowering species. This study assesses the possibility of growing autumn-to-spring-flowering bulbs and forbs with Bermudagrass, to provide ecosystem services in urban areas. Eight geophytes and 18 forbs were incorporated into a mature turf of hybrid Bermudagrass, Cynodon dactylon × C. transvaalensis cv. "Tifway". At the same time, a commercial flowering mix was sown in the same conditions. Two different soil preparations, scalping and turf flaming, and two different nitrogen doses, 50 and 150 kg ha, were carried out before sowing and transplanting. The flowering plants were counted. All the bulbs and six of the 18 forbs were able to grow and flower in the first and second years. The commercial mix was in full bloom from April until the cutting time for the hybrid Bermudagrass, at the end of May. Adding the flowering species did not affect the healthy growth of the warm-season grass. The fertilization dose had no effect, while turf flaming led to a wider spread of Bellis perennis L. and Crocus spp. Several flower-visiting insects were observed in the spring.Source: LANDSCAPE AND ECOLOGICAL ENGINEERING, vol. 16, pp. 307-317
DOI: 10.1007/s11355-020-00423-w
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See at: ISTI Repository Open Access | Landscape and Ecological Engineering Restricted | CNR IRIS Restricted | CNR IRIS Restricted | CNR IRIS Restricted | link.springer.com Restricted


2022 Journal article Open Access OPEN
Short-term abandonment versus mowing in a mediterranean-temperate meadow: effects on floristic composition, plant functionality, and soil properties - a case study
Vannucchi F, Lazzeri V, Rosellini I, Scatena M, Caudai C, Bretzel F
Hay meadows are secondary grasslands maintained by mowing, and their ecological importance resides in the inherent biodiversity and carbon stocking. We investigated the plant community and soil properties of a sub humid acid grassland near the Fucecchio marshes (Italy), managed as a hay meadow, mowed once a year, and not fertilized. Part of the meadow had been abandoned for three years. We analysed the soil properties (i.e., organic carbon and total nitrogen content, available phosphorus, pH, cation-exchange capacity, texture, and conductibility) and the plant community structure (composition, functionality, and species richness) of the two sides of the meadow (mowed and abandoned). Our aim was to highlight the changes in soil properties and vegetation community, and to find out to what extent abandonment can affect those dynamics. Our results showed that after short-term abandonment, soil pH, C and N increased; litter biomass and perennial forbs increased; and annual forbs decreased. New species colonising after abandonment, thus enriching the flora, may keep spreading and eventually hinder the growth of the specialists if mowing is not resumed. Certain valuable meadow habitats need constant human intervention to maintain their peculiar vegetation, most especially if they are a buffer zone in the proximity of natural protected areas.Source: AGRICULTURE, vol. 12 (issue 1)
DOI: 10.3390/agriculture12010078
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See at: CNR IRIS Open Access | ISTI Repository Open Access | www.mdpi.com Open Access | CNR IRIS Restricted


2022 Journal article Open Access OPEN
Low productivity substrate leads to functional diversification of green roof plant assemblage
Vannucchi F, Buoncristiano A, Scatena M, Caudai C, Bretzel F
Green roofs are roof free spaces where living organisms can find an appropriate habitat to colonise. The establishment of plant species with different functionality can enhance biodiversity and provide ecosystem services. However, drought and nutrient availability can affect the plant development. The extensive green roof was set up in Pisa (Italy) in 2014, 12 modules of 10 cm depth were filled with three substrates composed of compost from municipal mixed waste, pelletised paper sludge, and commercial tephra product (Vulcaflor), as follows: Vulcaflor + compost, Vulcaflor + pellet + compost, and Vulcaflor + pellet, characterised by decreasing level of nitrogen content. The species planted in 2014 were chosen from the herbaceous spontaneous vegetation of urban and rural swards not often mowed, plus two sedum species. After the establishment phase, the green roof community was progressively dominated by Sedum species and other species were seeded in 2016. In 2018-19 the plant functional types and the community structure were monitored. Besides seasonal fluctuations, nitrogen shaped the composition of the community, and Sedum species showed high cover values in nitrogen-richer substrates. Annual forbs colonised the plots with a lower nitrogen content. In summer, the number of species drastically fell, and Sedum album was dominant in the three substrates. Seedling recruitment regenerated the community in the cooler season, increasing the diversity in the poor substrate. The scarcity of nitrogen led to the development of stress-tolerator annuals increasing the biodiversity in the rainy-cool season. Annual species constitute a transient seed bank which enables the system to regenerate when rain follows periods of heat and drought.Source: ECOLOGICAL ENGINEERING, vol. 176
DOI: 10.1016/j.ecoleng.2022.106547
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See at: ISTI Repository Open Access | CNR IRIS Restricted | CNR IRIS Restricted | CNR IRIS Restricted | www.sciencedirect.com Restricted


2023 Journal article Open Access OPEN
Mediterranean extensive green roof self-sustainability mediated by substrate composition and plant strategy
Vannucchi F., Bibbiani C., Caudai C., Bretzel F.
In the cultivation of extensive green roofs (EGRs), substrate composition is a key aspect together with the evaluation of suitable recycled materials. Recycling materials as amendments can improve the establishment of a self-sustainable EGR, thus providing ecosystem services and benefits from a circular economy and climate change perspective. This study investigates the effects of compost and paper sludge on water retention, substrate temperature attenuation and plant diversity in an EGR experiment. The substrates were composed of tephra (V), compost (C) and paper sludge (P) as follows: VC, as control, VPC and VP. Herbaceous species with different ecological functionality (succulents, annuals, perennials, legumes, geophytes) were sown and/or transplanted with no cultivation inputs. Plant community composition -abundance- and diversity-richness-, substrate water retention and temperature were analyzed. The VPC and VC had the same average substrate temperature, with values lower than VP. The water retention capacity was higher in VC, thanks to the presence of compost. The substrate with paper sludge (VPC and VP) showed the highest species diversity. The VPC substrate was the best compromise for EGR temperature mitigation and plant diversity improvement. Plant functional types in EGRs can be increased, and thus the biodiversity, by modulating the quality and percentage of amendments. The substrate composition can also affect water retention and substrate temperature. In addition, the use of recycling paper sludge in growing media is a winning strategy to reduce waste.Source: HORTICULTURAE, vol. 9 (issue 10)
DOI: 10.3390/horticulturae9101117
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See at: CNR IRIS Open Access | ISTI Repository Open Access | www.mdpi.com Open Access | CNR IRIS Restricted


2012 Conference article Open Access OPEN
Evaluating Hebbian self-organizing memories for lexical representation and access
Marzi Claudia, Ferro Marcello, Caudai Claudia, Pirrelli Vito
The lexicon is the store of words in long-term memory. Any attempt at modelling lexical competence must take issues of string storage seriously. In the present contribution, we discuss a few desiderata that any biologically-inspired computational model of the mental lexicon has to meet, and detail a multi-task evaluation protocol for their assessment. The proposed protocol is applied to a novel computational architecture for lexical storage and acquisition, the "Topological Temporal Hebbian SOMs" (T2HSOMs), which are grids of topologically organised memory nodes with dedicated sensitivity to time-bound sequences of letters. These maps can provide a rigorous and testable conceptual framework within which to provide a comprehensive, multi-task protocol for testing the performance of Hebbian self-organising memories, and a comprehensive picture of the complex dynamics between lexical processing and the acquisition of morphological structure.

See at: CNR IRIS Open Access | www.lrec-conf.org Open Access | CNR IRIS Restricted


2016 Journal article Open Access OPEN
Computational estimation of chromosome structure
Caudai C, Salerno E
Research performed at ISTI-CNR in the framework of the national Flagship Project InterOmics includes the development of algorithms to reconstruct the chromosome structure from "chromosome conformation capture" data. One algorithm now being tested has already produced interesting results. Unlike most popular techniques, it does not derive a classical distance-to-geometry problem from the original contact data, and applies an efficient multiresolution approach to the genome under study.Source: ERCIM NEWS, vol. 104, pp. 21-22

See at: ercim-news.ercim.eu Open Access | CNR IRIS Open Access | CNR IRIS Restricted


2016 Software Metadata Only Access
Reconstruction of 3D chromatin structure from chromosome conformation capture data (Release 2.0)
Salerno E, Caudai C
This Python code provides an estimate of the 3D structure of the chromatin fibre in cell nuclei from the contact frequency data produced by a 'Chromosome conformation capture' experiment. The only input required is a text file containing a general real matrix of contact frequencies. The related genomic resolution, along with a few geometric parameters and the parameters for tuning the estimation algorithm must be set in advance in a special section of the source code. The whole fibre is divided in independent segments, whose structures are estimated and modelled as single elements of a lower-resolution fibre that is treated recursively in the same way, until it cannot be divided anymore into independent segments. The full-resolution chain is then reconstructed by another recursive procedure.

See at: CNR IRIS Restricted


2016 Software Metadata Only Access
Reconstruction of 3D chromatin structure from chromosome conformation capture data (Release 3.1)
Salerno E, Caudai C
This Python code has a command-line and a GUI versions, and provides an estimate of the 3D structure of the chromatin fibre in cell nuclei from the contact frequency data produced by a 'Chromosome conformation capture' experiment. The only input required is a text file containing a general real matrix of contact frequencies. In the command-line version, the related genomic resolution, along with a few geometric parameters and the parameters for tuning the estimation algorithm must be set in advance in a special section of the source code. In the GUI version, all the tuneable parameters are made available in the user interface. The whole fibre is divided in independent segments, whose structures are estimated and modelled as single elements of a lower-resolution fibre that is treated recursively in the same way, until it cannot be divided anymore into independent segments. The full-resolution chain is then reconstructed by another recursive procedure. See the Readme file and the cited references for more detail.DOI: 10.13140/rg.2.2.35785.13923
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See at: CNR IRIS Restricted


2017 Journal article Open Access OPEN
The SENSEable Pisa project: citizen-participation in monitoring acoustic climate of Mediterranean city centres
Vinci B, Tonacci A, Caudai C, De Rosa P, Nencini L, Pratali L
The concept of urban sustainability and liveability closely depends on multi-level approaches to environmental issues. The ultimate goal in the field of noise management is to involve citizens and facilitate their participation in urban environmental decisions. The SENSEable Pisa project, based on the concept of Real-Time City and Smart City, presents an acoustic urban monitoring system based on a low-cost data acquisition method for a pervasive outdoor noise measurement. The system is based on the use of noise sensors located on private houses in the centre of Pisa, which provide a good model for the current acoustic climate of Mediterranean city centres. In this study, SENSEable acquisitions show a strong anthropogenic component not revealed by public strategic maps. The anthropogenic component, commonly known as movida, becomes increasingly critical in Mediterranean cities, therefore, it is necessary to explore methods highlighting this new source and to adopt strategies for the creation of reliable noise pollution maps.Source: CLEAN, vol. 45 (issue 7)
DOI: 10.1002/clen.201600137
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See at: CNR IRIS Open Access | onlinelibrary.wiley.com Open Access | ISTI Repository Open Access | CLEAN - Soil Air Water Restricted | CNR IRIS Restricted | CNR IRIS Restricted


2018 Software Open Access OPEN
ChromStruct v4.2 - Reconstruction of 3D chromatin structure from chromosome conformation capture data
Salerno E, Caudai C
This Python (v.2.7.10) code provides an estimate of the 3D structure of the chromatin fibre in cell nuclei from the contact frequency data produced by a 'Chromosome conformation capture' experiment. The only input required is a text file containing a general real matrix of contact frequencies. The code features a GUI where all the tuneable parameters are made available to the user. The fibre is divided in independent segments whose structures are first estimated separately and then modelled as single elements of a lower-resolution fibre, which is treated iteratively in the same way until it cannot be divided anymore into independent segments. The full-resolution chain is then reconstructed by another iterative procedure. See the Readme file and the cited references for more detail.

See at: CNR IRIS Open Access | www.researchgate.net Open Access | CNR IRIS Restricted


2024 Other Open Access OPEN
U-ProBE: a graphical Python interface to handle uncertainties in deep learning models
Bandini L., Bacciu D., Del Corso G., Caudai C.
La piattaforma U-Probe mira ad essere un supporto ad un crescente numero di utilizzatori che hanno necessità di valutare le performances di un modello e soprat- tutto la sua incertezza. Per questo motivo la piattaforma è dotata di una intuitiva interfaccia grafica semplice da utilizzare anche per i non addetti ai lavori. L’analisi dell’incertezza delle predizioni di un modello di Machine Learning o Deep Learning può essere effettuata utilizzando varie tecniche. Alcune di queste sono intrusive (anche dette by design), tali tecniche vanno a modificare l’architettura in- troducendo strumenti probabilistici che possono fornire importanti indicazioni sulle caratteristiche delle predizioni, a livello di affidabilità e incertezza. Tali tecniche comprendono ad esempio le Bayesian Neural Networks, i Variational Autoencoders ed i Deep Gaussian Processes. Sono tecniche molto performanti, sia nel mitigare l’overfitting che nell’uncertainty quantification, di contro sono però molto costose e richiedono molte risorse di calcolo e di tempo per l’allenamento dei modelli. Esistono poi le tecniche semi-intrusive, i cui più conosciuti rappresentanti sono i Deep En- semble; esse rappresentano una ampia classe di approcci che in generale combinano più modelli secondo criteri specifici in modo da valutare l’efficienza, l’incertezza e l’affidabilità delle predizioni senza interferire troppo con le architetture di partenza, ma richiedendo comunque un ampio dispendio di risorse. In questo lavoro abbiamo deciso di utilizzare per i nostri scopi esclusivamente metodi post-hoc, cioè non intrusivi, come il Trust Score ed il Monte Carlo Dropout, che sono in grado di fare efficaci valutazioni sull’incertezza delle predizioni quando il modello è stato già allenato, senza andare a interferire con le fasi di apprendimento o a modificare i parametri già imparati dal modello durante la back propagation. Tali metodi sono leggermente meno performanti dei metodi intrusivi, ma hanno il vantaggio di essere estremamente più rapidi e meno costosi.

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2008 Journal article Metadata Only Access
Using Blender for molecular animation and scientific representation
Zoppè Monica, Yuri Porozov, Raluca Andrei, Stefano Cianchetta, Maria Francesca Zini, Tiziana Loni, Claudia Caudai, Marco Callieri
The inside of a cell is a nanoworld in which life happens at tiny scale and high speed: hundreds of protein characters (minute as ants or large as elephants) play their roles in several different and fascinating environments, as varied as forest and desert, ocean and metropolis. Biologists have revealed the events of inner life using experimental quantitative and qualitative techniques and describe them in (difficult) scientific reports. We want to bring the beauty of biology to everyone's reach, using Blender in a rigorous but at the same time creative way. We have produced scripts to import crystallographic and NMR information from scientific databases, and are in the process of developing algorithms to obtain animations from still (3D) images. We also intend to use creative renderings in order to convey information about the physical and chemical properties of the subcellular environments and of the surface of each component in the cell. Our work has the primary aim of enabling scientists to observe directly the objects of their study, by showing the kinetics and conformational changes as animations, but it can be of great value for teaching, for the spread of scientific knowledge and thinking, and provide artists with inspiration as representation of life, well beyond the DNA spiral.

See at: CNR IRIS Restricted


2015 Other Open Access OPEN
Architettura ISTI per il progetto INTEROMICS
Caudai C, Righi M, Tampucci M
Il progetto INTEROMICS (Sviluppo di una piattaforma integrata per l'applicazione delle scienze "omiche" alla definizione dei biomarcatori e profili diagnostici, predittivi e teranostici) prevede lo sviluppo delle competenze per l'intera filiera delle "scienze omiche", con particolare riferimento alla genomica, proteomica, bioinformatica e system biology. Il laboratorio concentra le sue attività nel campo della bioinformatica e dell'analisi delle immagini per impieghi in biologia.

See at: CNR IRIS Open Access | ISTI Repository Open Access | CNR IRIS Restricted


2014 Conference article Open Access OPEN
A statistical approach to infer 3D chromatin structure
Caudai C, Salerno E, Zoppè M, Tonazzini A
Our goal in the framework of the Italian Flagship Project InterOmics is to reconstruct a set of plausible chromatin configurations from Chromosome Conformation Capture data. To this end, we rely on a simulated annealing algorithm that samples the solution space defined by a data-fit function and a multiscale chromatin model. The data-fit only accounts for the largest, most reliable contact frequencies, in order to avoid deriving distances inconsistent with the Euclidean geometry. At each scale, the chromatin model consists in a chain of partially penetrable beads whose properties (bead sizes, elasticity, curvature, etc.) can be constrained through biochemical and biological knowledge. During the annealing process, the model configuration is evolved through quaternions rather than the usual Euler matrices, as this offers a number of advantages in terms of composition of successive perturbations and automatic satisfaction of the constraints. The output of the annealing scheme is not unique due to the degrees of freedom left by the geometrical constraints. This allows us to obtain multiple configurations compatible with both the data and the prior knowledge. We are validating our method by applying it to real Hi-C data from the long arm of the human Chromosome 1. The mean-square Euclidean distances computed from our results as functions of the genomic distances support previous experimental results indicating that highly expressed genomic regions are less compact than poorly transcribed regions.

See at: CNR IRIS Open Access | www.bmtl.it Open Access | CNR IRIS Restricted


2014 Conference article Open Access OPEN
A multiscale model for 3D chromatin structure estimation using quaternions
Caudai C, Salerno E, Zoppè M, Tonazzini A
We present a method to reconstruct a set of plausible chromatin configurations from contact data obtained through Chromosome Conformation Capture techniques. We do not look for a unique configuration because the experimental data are not derived from a single cell, but from millions of cells. As opposed to most popular methods, we do not translate contact frequencies deterministically into distances, since this often produces structures that are not consistent with the Euclidean geometry. We build a data-fit function directly from the pairs of loci with the largest contact frequencies, assuming that they are likely to be in contact, and neglecting the pairs with very low or zero contact frequencies, as we cannot infer anything about their mutual distances. To obtain configurations consistent with both the data and the available biological knowledge, we introduce a chromatin model that can be suitably constrained. Taking advantage of the block structure of the contact matrix, we adopt a multiscale approach where the chromatin fiber is divided into a number of segments that can be treated in parallel. Each of them is modeled as a chain of partially penetrable beads whose properties (bead sizes, elasticity, curvature, etc.) can be constrained on the basis of biochemical and biological knowledge. The model parameters can easily be extended to exploit any further information available. Once the individual structures are reconstructed, each segment can be treated as an element of a new chain, and the procedure can be repeated recursively at different scales. Our algorithm samples the solution space generated by the data-fit function through a Monte Carlo method. At each step, the subchains are perturbed by using quaternions. This is an extension of the complex algebra that offers a number of advantages, by avoiding singularities typical in the Euler matrix formalism, facilitating the composition of rotations, and allowing for a continuous evolution of the structure that is intrinsically compatible with the topological constraints. To validate the new method, we applied it to real Hi-C data available online (Lieberman-Aiden et al., 2009). In particular, we analyzed the contact frequency data from the long arm of the human Chromosome 1 with a maximum resolution of 100 kb, obtaining a number of output configurations. For each configuration, the first division of the overall fiber included 25 topological domains (Dixon et al., 2012). The reconstructed structures were then assumed as single elements of a new chain (with nonuniform resolution), whose mutual interactions were estimated by the same algorithm. The output structures should be validated biologically. As a first test, we computed the relationships between the genomic and Euclidean distances of pairs of loci in the entire chains reconstructed. Our results are compatible with the analogous plots, derived from FISH experiments on the same genomic region, found in Mateos-Langerak et al. (2009).

See at: CNR IRIS Open Access | www.eccb14.org Open Access | CNR IRIS Restricted


2015 Other Open Access OPEN
InterOmics - Reconstructing 3D chromatin structure from chromosome conformation capture data.
Caudai C, Salerno E, Zoppè M, Tonazzini A
Dna is the central repository of information to keep cells and organisms alive. In human cells, the 46 chromosomes amount to a length of about 2 m, with a diameter of 2 nm, and are packed in a way that allows for access by transcription, replication and repair machinery, fitting within a globular nucleus with a radius of 5000 to 10000 nm. Efficiency of packing is obtained by several levels of packing mechanisms (Figure 1), both general (due to general principles, irrespective of Dna sequence) and speci fic, i.e. mediated by proteins that recognize specifi c motives (sequences) and bring in close proximity parts of Dna that may be very distant in the genomic sequence. In both cases, general packing and specifi c aggregation, the underlying mechanisms are not entirely described or understood. The fi rst level, mediated by histon octamers, produces a ber of 11 nm, which in turn is organized into a 30 nm-wide structure. Further packing is at work in cells, and the research community engaged in the study of chromatin conformation is producing increasing knowledge that will finally allow for a clear vision of the nuclear machinery that regulates Dna metabolism.

See at: ISTI Repository Open Access | CNR IRIS Restricted | CNR IRIS Restricted


2015 Journal article Open Access OPEN
Inferring 3D chromatin structure using a multiscale approach based on quaternions
Caudai C, Salerno E, Zoppè M, Tonazzini A
Background: The knowledge of the spatial organisation of the chromatin fibre in cell nuclei helps researchers to understand the nuclear machinery that regulates DNA activity. Recent experimental techniques of the type Chromosome Conformation Capture (3C, or similar) provide high-resolution, high-throughput data consisting in the number of times any possible pair of textsc{dna} fragments is found to be in contact, in a certain population of cells. As these data carry information on the structure of the chromatin fibre, several attempts have been made to use them to obtain high-resolution 3D reconstructions of entire chromosomes, or even an entire genome. The techniques proposed treat the data in different ways, possibly exploiting physical-geometric chromatin models. One popular strategy is to transform contact data into Euclidean distances between pairs of fragments, and then solve a classical distance-to-geometry problem. Results: We developed and tested a reconstruction technique that does not require translating contacts into distances, thus avoiding a number of related drawbacks. Also, we introduce a geometrical chromatin chain model that allows us to include sound biochemical and biological constraints in the problem. This model can be scaled at different genomic resolutions, where the structures of the coarser models are influenced by the reconstructions at finer resolutions. The search in the solution space is then performed by a classical simulated annealing, where the model is evolved efficiently through quaternion operators. The presence of appropriate constraints permits the less reliable data to be overlooked, so the result is a set of plausible chromatin configurations compatible with both the data and the prior knowledge. Conclusions: To test our method, we obtained a number of 3D chromatin configurations from Hi-C data available in the literature for the long arm of human chromosome 1, and validated their features against known properties of gene density and transcriptional activity. Our results are compatible with biological features not introduced {em a priori} in the problem: structurally different regions in our reconstructions highly correlate with functionally different regions as known from literature and genomic repositories.Source: BMC BIOINFORMATICS, vol. 16
DOI: 10.1186/s12859-015-0667-0
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See at: BMC Bioinformatics Open Access | BMC Bioinformatics Open Access | BMC Bioinformatics Open Access | CNR IRIS Open Access | ISTI Repository Open Access | www.biomedcentral.com Open Access | CNR IRIS Restricted