Nicolas Carels

• PhD
• Laboratory of Biological System Modeling at Oswaldo Cruz Foundation

We presented a method to find potential cancer attractors using single-cell RNA sequencing (scRNA-seq) data. We tested our method in a Glioblastoma Multiforme (GBM) dataset, an aggressive brain tumor presenting high heterogeneity. Using the cancer attractor concept, we argued that the GBM’s underlying dynamics could partially explain the observed h...

We presented a method to find potential cancer attractors using single-cell RNA sequencing (scRNA-seq) data. We tested our method in a Glioblastoma Multiforme (GBM) dataset, an aggressive brain tumor presenting high heterogeneity. Using the cancer attractor concept, we argued that the GBM's underlying dynamics could partially explain the observed h...

Simple Summary We show how the relationship between the sub-network entropy of malignant up-regulated genes in twelve different types of cancer, spanning the entire spectrum of 5-year overall survival rates, can serve as a benchmark for optimizing RNA-seq workflows. Assessing the Shannon entropy of sub-networks formed by malignant up-regulated gene...

Glioblastoma Multiforme is a brain tumor distinguished by its aggressiveness. We suggested that this aggressiveness leads single-cell RNA-sequence data (scRNA-seq) to span a representative portion of the cancer attractors domain. This conjecture allowed us to interpret the scRNA-seq heterogeneity as reflecting a representative trajectory within the...

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing o...

Environmental stresses, such as drought, have negative effects on crop yield. Drought is a stress whose impact tends to increase in some critical regions. However, the worldwide population is continuously increasing and climate change may affect its food supply in the upcoming years. Therefore, there is an ongoing effort to understand the molecular...

This report aims to enhance the understanding of Glioblastoma Multiforme (GBM) subtypes’ dynamics by exploring the association between ergodicity and GBM aggressiveness. We introduce new regulation functions to model the network dynamics and perform parameter estimation using centroids obtained from multiple clustering methods. Our findings demonst...

Since cancer is a genetic disease, studying gene regulatory networks related to this pathology offers the possibility of obtaining helpful information for therapeutic purposes. However, the complexity expressed by the interconnections between network components grows exponentially with the number of genes in the system. In this report, the Boolean...

Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, c...

The main hallmarks of cancer include sustaining proliferative signaling and resisting cell death. We analyzed the genes of the WNT pathway and seven cross-linked pathways that may explain the differences in aggressiveness among cancer types. We divided six cancer types (liver, lung, stomach, kidney, prostate, and thyroid) into classes of high (H) a...

Cancer is a genomic disease involving various intertwined pathways with complex cross-communication links. Conceptually, this complex interconnected system forms a network, which allows one to model the dynamic behavior of the elements that characterize it to describe the entire system's development in its various evolutionary stages of carcinogene...

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analy...

One aspect of personalized medicine is aiming at identifying specific targets for therapy considering the gene expression profile of each patient individually. The real-world implementation of this approach is better achieved by user-friendly bioinformatics systems for healthcare professionals. In this report, we present an online platform that end...

Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and Dipetalogaster maxima are all triatomines and potential vectors of the protozoan Trypanosoma cruzi responsible for human Chagas' disease. Considering that the T. cruzi's cycle occurs inside the triatomine digestive tract (TDT), the analysis of the TDT protein profile is an essential...

Personalized medicine aims at identifying specific targets for treatment considering the gene expression profile of each patient individually. We discuss the challenges for personalized oncology to take off and present a particular approach to it that we are developing. That is, the subtraction of RNA-seq data of tumoral and non-tumoral surrounding...

Cells in an organism interact with each other and with the environment through a complex set of signals, which triggers responses and activate cellular regulation mechanisms. Models obtained by computational mathematics for cellular signaling dynamics are used to understand factors and causes of deregulation of internal biological processes, which...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. T...

Cancer is a genetic disease for which traditional treatments cause harmful side effects. After two decades of genomics technological breakthroughs, personalized medicine is being used to improve treatment outcomes and mitigate side effects. In mathematical modeling, it has been proposed that cancer matches an attractor in Waddington's epigenetic la...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the ongoing pandemic of 2019 CoV disease (COVID-19), which is leading to 10-times more deaths then other public health emergencies of international concern provoked by highly pathogenic CoV from the years 2002 and 2012. Besides social isolation, identification...

This book presents a range of current research topics in biological network modeling, as well as its application in studies on human hosts, pathogens, and diseases. Systems biology is a rapidly expanding field that involves the study of biological systems through the mathematical modeling and analysis of large volumes of biological data. Gathering...

Traditional approaches to cancer therapy seek common molecular targets in tumors from different patients. However, molecular profiles differ between patients, and most tumors exhibit inherent heterogeneity. Hence, imprecise targeting commonly results in side effects, reduced efficacy, and drug resistance. By contrast, personalized medicine aims to...

We present a compilation on the evolutive processes that led to the gene emergence that should help readers who are not familiar with the subject to understand the mechanisms that might have shaped it over time. The main challenge in these processes is that they must be coherent with the emergence of self-reproducing systems from simple in- and org...

Physic nut (Jatropha curcas L.) is a tree in the family Euphorbiaceae whose members have been known for the production of important natural compounds for therapeutic applications. Physic nut is also one of the few important plant species whose genome has been fully sequenced under high scrutiny, mostly because it is a potential source of oil, which...

Serratia marcescens is a bacterium with the ability to colonize several niches, including some eukaryotic hosts. S. marcescens have been recently found in the gut of hematophagous insects that act as parasite vectors, such as Anopheles, Rhodnius, and Triatoma. While some S. marcescens strains have been reported as symbiotic or pathogenic to other i...

Average nucleotide identity between Serratia genomes, bacterial secretion systems, KEGG and Ano1 orthologous, gene islands, antibiotic resistance genes and one way ANOVA of trypanolytic activity.

Jatropha curcas, or physic nut, is a small tree that, in tropical climates, produces fruits with seeds containing ~38% oil. The physic nut has the potential to be highly productive and is amenable to subculture in vitro and to genetic modification. It also displays remarkable diversity and is relatively easy to cross hybridize within the genus. Tha...

The genus Fusarium contains some of the most studied and important species of plant pathogens that economically affect world agriculture and horticulture. Fusarium spp. are ubiquitous fungi widely distributed in soil, plants as well as in different organic substrates and are also considered as opportunistic human pathogens. The identification of sp...

This review focuses on how system biology may assist techniques that are used in pharmacological research, such as high-throughput screening, high-throughput analytical characterization of biological samples, preclinical and clinical trials, as well as targets and drug validation in order to reach patients at the lowest possible cost in a translati...

Translational medicine has been leveraging new technologies and tools for data analysis to promote the development of new treatments. Integration of translational medicine with system biology allows the study of diseases from a holistic perspective. Cancer is a disease of cell regulation that affects genome integrity and ultimately disrupts cell ho...

With cellular reprogramming, it is possible to convert a cell from one phenotype to another without necessarily passing through a pluripotent state. This perspective is opening many interesting fields in the world of research and biomedical applications. This essay provides a concise description of the purpose of this technique, its evolution, math...

Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network reorganization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identifi...

Systems Biology is a rapidly expanding field and comprises the study of biological systems through mathematical modeling and the analysis of large volumes of biological data. This book presents the theoretical foundations of Systems Biology, as well as its application in studies on human hosts, pathogens and associated diseases. This book presents...

The digestive tract of triatomines (DTT) is an ecological niche favored by microbiota whose enzymatic profile is adapted to the specific substrate availability in this medium. This report describes the molecular enzymatic properties that promote bacterial prominence in the DTT. The microbiota composition was assessed previously based on 16S ribosom...

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic fun...

Trypanosoma cruzi is the protozoan pathogen responsible for Chagas disease, which is a major public health problem in tropical and subtropical regions of developing countries and particularly in Brazil. Despite many studies, there is no efficient treatment against Chagas disease, and the search for new therapeutic targets specific to T. cruzi is cr...

Jatropha curcas L. oil has been shown to be suitable for the production of biodiesel. However, this species has not been domesticated yet. Genetic breeding through conventional methods is time consuming and costly, hence, genetic transformation could contribute positively to the improvement of interesting traits. Although in vitro regeneration and...

Background The selection of suitable internal control genes is crucial for proper interpretation of real-time PCR data. Here we outline a strategy to identify housekeeping genes that could serve as suitable internal control for comparative analyses of gene expression data in breast cancer cell lines and tissues obtained by high throughput sequencin...

Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network re-organization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identif...

In this review, we report on breast cancer's molecular features and on how high throughput technologies are helping in understanding the dynamics of tumorigenesis and cancer progression with the aim of developing precision medicine methods. We first address the current state of the art in breast cancer therapies and challenges in order to progress...

Background: In this report, we show how entropy computation can be applied to the characterization of a protein-protein interaction networks to assist the selection of personalized chemotherapeutic strategy for cancer treatment. Methods: With seven malignant (BT-20, BT-474, MDA-MB-231, MDA-MB-468, MCF-7, T-47D, ZR-75-1) and one healthy (MCF10A) cel...

We present a comprehensive compilation of genomic structure evolution that should help the reader that is not familiarized with genomics to understand the mechanisms that are shaping its structures over time. We believe that this understanding is essential to work with genomics in the sense that it should help to formulate productive hypothesis for...

Physiological responses, developmental programs, and cellular functions depend on complex networks of interactions at different scales and levels. Systems biology unites biochemical, genetic, and molecular approaches to generate omics data that can be analyzed and used in computational models to uncover these global networks. Various approaches, in...

Chagas disease is caused by Trypanosoma cruzi, which is transmitted by triatomine vectors. The northeastern region of Brazil is endemic for Chagas disease and has the largest diversity of triatomine species. T. cruzi development in its triatomine vector depends on diverse factors, including the composition of bacterial gut microbiota. We characteri...

Purine bias, which is usually referred to as an “ancestral codon”, is known to result in short-range correlations between nucleotides in coding sequences, and it is common in all species. We demonstrate that RWY is a more appropriate pattern than the classical RNY, and purine bias (Rrr) is the product of a network of nucleotide compensations induce...

Since the world faced the petroleum crisis in the 1970s and people started to realize the limitation of fossil energy resources coupled with concerns over the effects of increasing carbon dioxide in the atmosphere, major efforts were devoted to the search for alternative energy sources. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In this report, we describe a strategy for the optimized selection of protein targets suitable for drug development against neoplastic diseases taking the particular case of breast can-cer as an example. We combined human interactome and transcriptome data from malig-nant and control cell lines because highly connected proteins that are up-regulate...

Development of dedicated perennial crops has been indicated as a strategic action to meet the growing demand for biofuels. Breeding of perennial crops,however, is often time- and resource-consuming. As genomics offers a platform from which to learn more about the relationships of genes and phenotypes,its operational use in the context of breeding p...

For this report, we analyzed protein secondary structures in relation to the statistics of three nucleotide codon positions. The purpose of this investigation was to find which properties of the ribosome, tRNA or protein level, could explain the purine bias (Rrr) as it is observed in coding DNA. We found that the Rrr pattern is the consequence of a...

Chagas disease is a trypanosomiasis whose causative agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous insects known as triatomines and affects a large proportion of South America. The digestive tract of the insect vectors in which T. cruzi develops constitutes a dynamic environment that affects the d...

In this report, we revisited the classification of coding sequences (CDS) based on nucleotide statistics using the Universal Feature Method (UFM). We show that the rules (i) G1>G2 (G1 and G2 are the guanine levels in 1st and 2nd position of contiguous DNA triplets, respectively) and (ii) T1<A2 (T1 and A2 are the thymine and adenine levels in 1st an...

Protein function is conserved in protein domains. These are able to perform independent folding and are approximately conserved among species. A major goal in the study of proteins is the identification and characterization of domains and domain families. Some algorithms have appeared in the scientific literature to obtain information on domains fr...

In this study, we investigated the modalities of coding open reading frame (cORF) classification of expressed sequence tags (EST) by using the universal feature method (UFM). The UFM algorithm is based on the scoring of purine bias (Rrr) and stop codon frequencies. UFM classifies ORFs as coding or non-coding through a score based on 5 factors: (i)...

Global warming, population, environmental degradation and food production are serious concerns to the well being of mankind and our planet. Development of sustainable energy resources is an essential component to many of these problems. Of these bioenergy holds the greatest promise to contribute significantly to reduce petroleum consumption and gre...

Renewable sources of energy are now necessary. Biodiesel is an attractive alternative to fossil oil. However, this type of energy is largely based on three industrial food crops for its worldwide supply and will remain marginal in the long term if sources are not diversified. Because of this need, the international community is now searching for se...

Factors, such as overpopulation, resource reduction and loss of biodiversity are considered most threatening for humanity and their interaction in the history of mankind are shortly revisited. These are the driving forces that led governments worldwide to the implementation of renewable energies. Among, the renewable energies that started to contri...

Chagas disease is one of the most important endemic diseases of South and Central America. Its causative agent is the protozoan Trypanosoma cruzi, which is transmitted to humans by blood-feeding insects known as triatomine bugs. These vectors mainly belong to Rhodnius, Triatoma and Panstrongylus genera of Reduviidae. The bacterial communities in th...

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