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Article ; Online: Cell annotation using scRNA-seq data

Daniela Senra / Nara Guisoni / Luis Diambra

MethodsX, Vol 10, Iss , Pp 102179- (2023)

A protein-protein interaction network approach

2023

Abstract: Pathway analysis is an important step in the interpretation of single cell transcriptomic data, as it provides powerful information to detect which cellular processes are active in each individual cell. We have recently developed a protein-protein ... ...

Abstract	Pathway analysis is an important step in the interpretation of single cell transcriptomic data, as it provides powerful information to detect which cellular processes are active in each individual cell. We have recently developed a protein-protein interaction network-based framework to quantify pluripotency associated pathways from scRNA-seq data. On this occasion, we extend this approach to quantify the activity of a pathway associated with any biological process, or even any list of genes. A systems-level characterization of pathway activities across multiple cell types provides a broadly applicable tool for the analysis of pathways in both healthy and disease conditions. Dysregulated cellular functions are a hallmark of a wide spectrum of human disorders, including cancer and autoimmune diseases. Here, we illustrate our method by analyzing various biological processes in healthy and cancer breast samples. Using this approach we found that tumor breast cells, even when they form a single group in the UMAP space, keep diverse biological programs active in a differentiated manner within the cluster. • We implement a protein-protein interaction network-based approach to quantify the activity of different biological processes. • The methodology can be used for cell annotation in scRNA-seq studies and is freely available as R package.
Keywords	scRNA-seq ; Protein-protein interaction networks ; Cell annotation ; Biological Processes ; Breast cancer ; Science ; Q
Subject code	612
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ORIGINS

Daniela Senra / Nara Guisoni / Luis Diambra

MethodsX, Vol 9, Iss , Pp 101778- (2022)

A protein network-based approach to quantify cell pluripotency from scRNA-seq data

2022

Abstract: Trajectory inference is a common application of scRNA-seq data. However, it is often necessary to previously determine the origin of the trajectories, the stem or progenitor cells. In this work, we propose a computational tool to quantify pluripotency ... ...

Abstract	Trajectory inference is a common application of scRNA-seq data. However, it is often necessary to previously determine the origin of the trajectories, the stem or progenitor cells. In this work, we propose a computational tool to quantify pluripotency from single cell transcriptomics data. This approach uses the protein-protein interaction (PPI) network associated with the differentiation process as a scaffold and the gene expression matrix to calculate a score that we call differentiation activity. This score reflects how active the differentiation network is in each cell. We benchmark the performance of our algorithm with two previously published tools, LandSCENT (Chen et al., 2019) and CytoTRACE (Gulati et al., 2020), for four healthy human data sets: breast, colon, hematopoietic and lung. We show that our algorithm is more efficient than LandSCENT and requires less RAM memory than the other programs. We also illustrate a complete workflow from the count matrix to trajectory inference using the breast data set. • ORIGINS is a methodology to quantify pluripotency from scRNA-seq data implemented as a freely available R package. • ORIGINS uses the protein-protein interaction network associated with differentiation and the data set expression matrix to calculate a score (differentiation activity) that quantifies pluripotency for each cell.
Keywords	ORIGINS ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

Andres Mariano Alonso / Luis Diambra

Frontiers in Cell and Developmental Biology, Vol

2020 Volume 8

Abstract: Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In ...

Abstract	Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
Keywords	SARS-CoV-2 ; codon usage bias ; codon optimality ; translational control ; pathogeny ; vaccine design ; Biology (General) ; QH301-705.5 ; covid19
Subject code	572
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prediction of cell position using single-cell transcriptomic data

Andrés M. Alonso / Alejandra Carrea / Luis Diambra

F1000Research, Vol

an iterative procedure [version 2; peer review: 2 approved]

2020 Volume 8

Abstract: Single-cell sequencing reveals cellular heterogeneity but not cell localization. However, by combining single-cell transcriptomic data with a reference atlas of a small set of genes, it would be possible to predict the position of individual cells and ... ...

Abstract	Single-cell sequencing reveals cellular heterogeneity but not cell localization. However, by combining single-cell transcriptomic data with a reference atlas of a small set of genes, it would be possible to predict the position of individual cells and reconstruct the spatial expression profile of thousands of genes reported in the single-cell study. With the purpose of developing new algorithms, the Dialogue for Reverse Engineering Assessments and Methods (DREAM) consortium organized a crowd-sourced competition known as DREAM Single Cell Transcriptomics Challenge (SCTC). Within this context, we describe here our proposed procedures for adequate reference genes selection, and an iterative procedure to predict spatial expression profile of other genes.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gene target discovery with network analysis in Toxoplasma gondii

Andres M. Alonso / Maria M. Corvi / Luis Diambra

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract Infectious diseases are of great relevance for global health, but needed drugs and vaccines have not been developed yet or are not effective in many cases. In fact, traditional scientific approaches with intense focus on individual genes or ... ...

Abstract	Abstract Infectious diseases are of great relevance for global health, but needed drugs and vaccines have not been developed yet or are not effective in many cases. In fact, traditional scientific approaches with intense focus on individual genes or proteins have not been successful in providing new treatments. Hence, innovations in technology and computational methods provide new tools to further understand complex biological systems such as pathogen biology. In this paper, we apply a gene regulatory network approach to analyze transcriptomic data of the parasite Toxoplasma gondii. By means of an optimization procedure, the phenotypic transitions between the stages associated with the life cycle of T. gondii were embedded into the dynamics of a gene regulatory network. Thus, through this methodology we were able to reconstruct a gene regulatory network able to emulate the life cycle of the pathogen. The community network analysis has revealed that nodes of the network can be organized in seven communities which allow us to assign putative functions to 338 previously uncharacterized genes, 25 of which are predicted as new pathogenic factors. Furthermore, we identified a small gene circuit that drives a series of phenotypic transitions that characterize the life cycle of this pathogen. These new findings can contribute to the understanding of parasite pathogenesis.
Keywords	Medicine ; R ; Science ; Q
Subject code	000
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systems Biology Approach to Model the Life Cycle of Trypanosoma cruzi.

Alejandra Carrea / Luis Diambra

PLoS ONE, Vol 11, Iss 1, p e

2016 Volume 0146947

Abstract: Due to recent advances in reprogramming cell phenotypes, many efforts have been dedicated to developing reverse engineering procedures for the identification of gene regulatory networks that emulate dynamical properties associated with the cell fates of ... ...

Abstract	Due to recent advances in reprogramming cell phenotypes, many efforts have been dedicated to developing reverse engineering procedures for the identification of gene regulatory networks that emulate dynamical properties associated with the cell fates of a given biological system. In this work, we propose a systems biology approach for the reconstruction of the gene regulatory network underlying the dynamics of the Trypanosoma cruzi's life cycle. By means of an optimisation procedure, we embedded the steady state maintenance, and the known phenotypic transitions between these steady states in response to environmental cues, into the dynamics of a gene network model. In the resulting network architecture we identified a small subnetwork, formed by seven interconnected nodes, that controls the parasite's life cycle. The present approach could be useful for better understanding other single cell organisms with multiple developmental stages.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modeling the emergence of circadian rhythms in a clock neuron network.

Luis Diambra / Coraci P Malta

PLoS ONE, Vol 7, Iss 3, p e

2012 Volume 33912

Abstract: Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in ... ...

Abstract	Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Abortive and propagating intracellular calcium waves

Nara Guisoni / Paola Ferrero / Carla Layana / Luis Diambra

PLoS ONE, Vol 10, Iss 1, p e

analysis from a hybrid model.

2015 Volume 0115187

Abstract: The functional properties of inositol(1,4,5)-triphosphate (IP3) receptors allow a variety of intracellular Ca(2+) phenomena. In this way, global phenomena, such as propagating and abortive Ca(2+) waves, as well as local events such as puffs, have been ... ...

Abstract	The functional properties of inositol(1,4,5)-triphosphate (IP3) receptors allow a variety of intracellular Ca(2+) phenomena. In this way, global phenomena, such as propagating and abortive Ca(2+) waves, as well as local events such as puffs, have been observed. Several experimental studies suggest that many features of global phenomena (e.g., frequency, amplitude, speed wave) depend on the interplay of biophysical processes such as diffusion, buffering, efflux and influx rates, which in turn depend on parameters such as buffer concentration, Ca(2+) pump density, cytosolic IP3 level, and intercluster distance. Besides, it is known that cells are able to modify some of these parameters in order to regulate the Ca(2+) signaling. By using a hybrid model, we analyzed different features of the hierarchy of calcium events as a function of two relevant parameters for the calcium signaling, the intercluster distance and the pump strength or intensity. In the space spanned by these two parameters, we found two modes of calcium dynamics, one dominated by abortive calcium waves and the other by propagating waves. Smaller distances between the release sites promote propagating calcium waves, while the increase of the efflux rate makes the transition from propagating to abortive waves occur at lower values of intercluster distance. We determined the frontier between these two modes, in the parameter space defined by the intercluster distance and the pump strength. Furthermore, we found that the velocity of simulated calcium waves accomplishes Luther's law, and that an effective rate constant for autocatalytic calcium production decays linearly with both the intercluster distance and the pump strength.
Keywords	Medicine ; R ; Science ; Q
Subject code	535
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Time-course analysis of cyanobacterium transcriptome

Carla Layana / Luis Diambra

PLoS ONE, Vol 6, Iss 10, p e

detecting oscillatory genes.

2011 Volume 26291

Abstract: The microarray technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining these data one can identify the dynamics of the gene expression time series. The detection of genes that are periodically expressed is ...

Abstract	The microarray technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining these data one can identify the dynamics of the gene expression time series. The detection of genes that are periodically expressed is an important step that allows us to study the regulatory mechanisms associated with the circadian cycle. The problem of finding periodicity in biological time series poses many challenges. Such challenge occurs due to the fact that the observed time series usually exhibit non-idealities, such as noise, short length, outliers and unevenly sampled time points. Consequently, the method for finding periodicity should preferably be robust against such anomalies in the data. In this paper, we propose a general and robust procedure for identifying genes with a periodic signature at a given significance level. This identification method is based on autoregressive models and the information theory. By using simulated data we show that the suggested method is capable of identifying rhythmic profiles even in the presence of noise and when the number of data points is small. By recourse of our analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Noise minimisation in gene expression switches.

Diana Monteoliva / Christina B McCarthy / Luis Diambra

PLoS ONE, Vol 8, Iss 12, p e

2013 Volume 84020

Abstract: Gene expression is subject to stochastic variation which leads to fluctuations in the rate of protein production. Recently, a study in yeast at a genomic scale showed that, in some cases, gene expression variability alters phenotypes while, in other ... ...

Abstract	Gene expression is subject to stochastic variation which leads to fluctuations in the rate of protein production. Recently, a study in yeast at a genomic scale showed that, in some cases, gene expression variability alters phenotypes while, in other cases, these remain unchanged despite fluctuations in the expression of other genes. These studies suggested that noise in gene expression is a physiologically relevant trait and, to prevent harmful stochastic variation in the expression levels of some genes, it can be subject to minimisation. However, the mechanisms for noise minimisation are still unclear. In the present work, we analysed how noise expression depends on the architecture of the cis-regulatory system, in particular on the number of regulatory binding sites. Using analytical calculations and stochastic simulations, we found that the fluctuation level in noise expression decreased with the number of regulatory sites when regulatory transcription factors interacted with only one other bound transcription factor. In contrast, we observed that there was an optimal number of binding sites when transcription factors interacted with many bound transcription factors. This finding suggested a new mechanism for preventing large fluctuations in the expression of genes which are sensitive to the concentration of regulators.
Keywords	Medicine ; R ; Science ; Q
Subject code	612 ; 570
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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