75,679 research outputs found
Representing and analysing molecular and cellular function in the computer
Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model
ProtNN: Fast and Accurate Nearest Neighbor Protein Function Prediction based on Graph Embedding in Structural and Topological Space
Studying the function of proteins is important for understanding the
molecular mechanisms of life. The number of publicly available protein
structures has increasingly become extremely large. Still, the determination of
the function of a protein structure remains a difficult, costly, and time
consuming task. The difficulties are often due to the essential role of spatial
and topological structures in the determination of protein functions in living
cells. In this paper, we propose ProtNN, a novel approach for protein function
prediction. Given an unannotated protein structure and a set of annotated
proteins, ProtNN finds the nearest neighbor annotated structures based on
protein-graph pairwise similarities. Given a query protein, ProtNN finds the
nearest neighbor reference proteins based on a graph representation model and a
pairwise similarity between vector embedding of both query and reference
protein-graphs in structural and topological spaces. ProtNN assigns to the
query protein the function with the highest number of votes across the set of k
nearest neighbor reference proteins, where k is a user-defined parameter.
Experimental evaluation demonstrates that ProtNN is able to accurately classify
several datasets in an extremely fast runtime compared to state-of-the-art
approaches. We further show that ProtNN is able to scale up to a whole PDB
dataset in a single-process mode with no parallelization, with a gain of
thousands order of magnitude of runtime compared to state-of-the-art
approaches
Lipid storage and autophagy in melanoma cancer cells
Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ). An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3) lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK) and Phospho-mammalian Target of Rapamycin (P-mTOR) were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology
Computational analysis of a plant receptor interaction network
Trabajo fin de máster en Bioinformática y Biología ComputacionalIn all organisms, complex protein-protein interactions (PPI) networks control major
biological functions yet studying their structural features presents a major analytical
challenge. In plants, leucine-rich-repeat receptor kinases (LRR-RKs) are key in sensing
and transmitting non-self as well as self-signals from the cell surface. As such, LRR-RKs
have both developmental and immune functions that allow plants to make the most of their
environments. In the model organism in plant molecular biology, Arabidopsis thaliana,
most LRR-RKs are still represented by biochemically and genetically uncharacterized
receptors. To fix this an LRR-based Cell Surface Interaction (CSI LRR ) network was
obtained in 2018, a protein-protein interaction network of the extracellular domain of 170
LRR-RKs that contains 567 bidirectional interactions. Several network analyses have been
performed with CSI LRR . However, these analyses have so far not considered the spatial and
temporal expression of its proteins. Neither has it been characterized in detail the role of
the extracellular domain (ECD) size in the network structure. Because of that, the objective
of the present work is to continue with more in depth analyses with the CSI LRR network.
This would provide important insights that will facilitate LRR-RKs function
characterization.
The first aim of this work is to test out the fit of the CSI LRR network to a scale-free
topology. To accomplish that, the degree distribution of the CSI LRR network was compared
with the degree distribution of the known network models of scale-free and random.
Additionally, three network attack algorithms were implemented and applied to these two
network models and the CSI LRR network to compare their behavior. However, since the
CSI LRR interaction data comes from an in vitro screening, there is no direct evidence
whether its protein-protein interactions occur inside the plant cells. To gain insight on how
the network composition changes depending on the transcriptional regulation, the
interaction data of the CSI LRR was integrated with 4 different RNA-Seq datasets related
with the network biological functions. To automatize this task a Python script was written.
Furthermore, it was evaluated the role of the LRR-RKs in the network structure depending
on the size of their extracellular domain (large or small). For that, centrality parameters
were measured, and size-targeted attacks performed. Finally, gene regulatory information
was integrated into the CSI LRR to classify the different network proteins according to the
function of the transcription factors that regulate its expression.
The results were that CSI LRR fits a power law degree distribution and approximates a scale-
free topology. Moreover, CSI LRR displays high resistance to random attacks and reduced
resistance to hub/bottleneck-directed attacks, similarly to scale-free network model. Also,
the integration of CSI LRR interaction data and RNA-Seq data suggests that the
transcriptional regulation of the network is more relevant for developmental programs than
for defense responses. Another result was that the LRR-RKs with a small ECD size have a
major role in the maintenance of the CSI LRR integrity. Lastly, it was hypothesized that the
integration of CSI LRR interaction data with predicted gene regulatory networks could shed
light upon the functioning of growth-immunity signaling crosstalk
Open source bioimage informatics for cell biology
Significant technical advances in imaging, molecular biology and genomics have fueled a revolution in cell biology, in that the molecular and structural processes of the cell are now visualized and measured routinely. Driving much of this recent development has been the advent of computational tools for the acquisition, visualization, analysis and dissemination of these datasets. These tools collectively make up a new subfield of computational biology called bioimage informatics, which is facilitated by open source approaches. We discuss why open source tools for image informatics in cell biology are needed, some of the key general attributes of what make an open source imaging application successful, and point to opportunities for further operability that should greatly accelerate future cell biology discovery
Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?
The organization and mining of malaria genomic and post-genomic data is
highly motivated by the necessity to predict and characterize new biological
targets and new drugs. Biological targets are sought in a biological space
designed from the genomic data from Plasmodium falciparum, but using also the
millions of genomic data from other species. Drug candidates are sought in a
chemical space containing the millions of small molecules stored in public and
private chemolibraries. Data management should therefore be as reliable and
versatile as possible. In this context, we examined five aspects of the
organization and mining of malaria genomic and post-genomic data: 1) the
comparison of protein sequences including compositionally atypical malaria
sequences, 2) the high throughput reconstruction of molecular phylogenies, 3)
the representation of biological processes particularly metabolic pathways, 4)
the versatile methods to integrate genomic data, biological representations and
functional profiling obtained from X-omic experiments after drug treatments and
5) the determination and prediction of protein structures and their molecular
docking with drug candidate structures. Progresses toward a grid-enabled
chemogenomic knowledge space are discussed.Comment: 43 pages, 4 figures, to appear in Malaria Journa
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Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion.
The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion
Complex Systems Science: Dreams of Universality, Reality of Interdisciplinarity
Using a large database (~ 215 000 records) of relevant articles, we
empirically study the "complex systems" field and its claims to find universal
principles applying to systems in general. The study of references shared by
the papers allows us to obtain a global point of view on the structure of this
highly interdisciplinary field. We show that its overall coherence does not
arise from a universal theory but instead from computational techniques and
fruitful adaptations of the idea of self-organization to specific systems. We
also find that communication between different disciplines goes through
specific "trading zones", ie sub-communities that create an interface around
specific tools (a DNA microchip) or concepts (a network).Comment: Journal of the American Society for Information Science and
Technology (2012) 10.1002/asi.2264
TumorML: Concept and requirements of an in silico cancer modelling markup language
This paper describes the initial groundwork carried out as part of the European Commission funded Transatlantic Tumor Model Repositories project, to develop a new markup language for computational cancer modelling, TumorML. In this paper we describe the motivations for such a language, arguing that current state-of-the-art biomodelling languages are not suited to the cancer modelling domain. We go on to describe the work that needs to be done to develop TumorML, the conceptual design, and a description of what existing markup languages will be used to compose the language specification
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