Bioinformatics

Bioinformatics: Cancer

Genome, transcriptome, and proteome of the adrenocortical tumor, neuroblastoma, and breast cancer
Pediatric adrenocortical AI

The project

Bioinformatics using Big Data from TCGA and other sources: A groundbreaking improvement in cancer research (adrenocortical carcinoma, neuroblastoma, and breast cancer). The use of different datasets for oncology research, like about the themes above, has been growing in the last years.

Bioinformatics data analysis is an essential in cancer genomics, enabling the interpretation of vast molecular data from the whole genome obtained using high-resolution technologies, such as next-generation sequencing (NGS). Bioinformatics tools can provide useful insights to answer some questions in pediatric oncology to identify possible prognostic biomarkers and therapeutical targets in adrenocortical tumor (ACT) and neuroblastoma, for example.

This monumental achievement provided scientists with an extensive blueprint of the human genetic code, offering unprecedented insights into human biology and disease. Since then, genomic research has witnessed exponential growth, leading to the emergence of numerous genomic databases that house vast amounts of genetic information. More recent genebanks used for cancer research was provided by The Cancer Genome Atlas (TCGA), which is a project aimed to catalogue the genetic mutations responsible for cancer using genome sequencing and bioinformatics, and St. Jude Cloud (the St. Jude Children’s Research Hospital database). The Research Institute database also includes in-house dataset from a cohort of participants.

This group is divided in three subgroups: one dedicated to study ACT, another to research neuroblastoma, and another researching leukemia.

About adrenocortical tumor (ACT)

Adrenocortical tumor (ACT) is a rare and aggressive tumor with limited treatment options and a poor prognosis. This disease presents a bimodal age incidence, being more prevalent in adults between 40 and 50 years old, and in infants up to 5 years old. Southern Brazil has the highest pediatric incidence of ACT worldwide (4.9 cases/million up to 15 years).

The research group at Pelé Pequeno Príncipe Research Institute has identified new therapeutical targets and prognostic markers by using datasets from The Cancer Genome Atlas, St. Jude Children’s Research Hospital datasets, and their own cohort analyses conducted at the Pequeno Príncipe Complex unit.

Objectives

The main objectives of this research project are to understand how transcription factors control other transcription factors in different types of cancer and to identify new germline variants implicated in tumorigenesis.

Partnerships

Federal University of Paraná (UFPR), in Brazil;
Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), in France; and
Thales Group, also in France.

About neuroblastoma

Neuroblastoma is an extracranial malignant solid tumor derived from embryonic neural crest cells and is responsible for the mortality of approximately 15% of all pediatric tumor cases. The usual age of onset of neuroblastoma is during early childhood, with the median age at diagnosis of 17 months. The International Neuroblastoma Staging System (INSS) categorizes patients into low, intermediate, and high-risk groups based on prognostic factors.

The overall survival rate for patients in the low-moderate risk group is greater than 95% by surgery alone, while the survival rate for high-risk children is less than 50%, with a higher risk of later metastasis and recurrence.

This research group uses bioinformatics tools to evaluate the genomes of cancer patients, focusing on non-coding RNAs (ncRNAs) and copy number alterations (CNAs) in breast tumors and pediatric nervous system tumors, including neuroblastomas and central nervous system (CNS) tumors. These projects are supported by national and international research agencies and involve a multidisciplinary team.

These studies have led to numerous publications that identify genetic variants, complex signaling pathways, network analyses, and integrated “omics” approaches.

Objective

The objective of this research project is to elucidate molecular mechanisms underlying cancer development and progression, treatment resistance, and potential therapeutic targets.

Partnerships

Oswaldo Cruz Foundation (Fiocruz), in Brazil;
State University of São Paulo, also in Brazil;
U.S. Food and Drug Administration (FDA);
U.S. National Institutes of Health (NIH);
Georgetown University Medical Center, in USA, among others.

About acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the most common type of cancer in children, accounting for 25% of all childhood cancers. Although the prognosis for children with this disease has significantly improved over time, there is a profound need for research to molecularly characterize its different subtypes and identify their specific biological features.

This research project is centered on utilizing bioinformatics approaches to identify molecular biomarkers and biological signatures of childhood leukemia, with the aim of identifying the pathological gene networks that contribute to leukemogenesis and influence therapeutic response in this disease.

Objective

The objective of the research project about leukemias is to explore the underlying biological mechanisms of acute lymphoblastic leukemia and to identify novel biomarkers, through the analysis of genome, transcriptome, and proteome data, in hope to pave the way to personalized treatment strategies and enhance prognostic evaluations of ALL patients.

Team cancer

Meet the team behind this research group.

Bonald Cavalcante de Figueiredo – Pelé Pequeno Príncipe Research Institute (lead researcher)
Mauro A. A. Castro – Federal University of Paraná (lead researcher)
Luciane R. Cavalli – Pelé Pequeno Príncipe Research Institute (lead researcher)
João C. D. Muzzi (postdoctoral student) - Pelé Pequeno Príncipe Research Institute
Jean S. S. Resende – Pelé Pequeno Príncipe Research Institute (PhD student)
Jéssica M. Magno – Federal University of Paraná (PhD Student)
Lana B. P. Querne – Federal University of Paraná
Talita H. B. Gomig – Federal University of Paraná
Juliana de Moura – Federal University of Paraná
Larissa M. Alvarenga – Federal University of Paraná
Igor S. Giner – Pelé Pequeno Príncipe Research Institute (Master Student)
Jonathan A. Back – Federal University of Paraná (Master Student)
Enzo Lalli – Institut de Pharmacologie Moléculaire et Cellulaire (IPMC, in France)
Mehdi Jendoubi – Thales Group (France)
Dupont Florent – Thales Group (France)
Roberto Rosati – Pelé Pequeno Príncipe Research Institute (lead researcher)
Saloê Bispo Poubel – Pelé Pequeno Príncipe Research Institute
Sara Cristina Lobo Alves – Pelé Pequeno Príncipe Research Institute
Liana Oliveira – Pelé Pequeno Príncipe Research Institute

Published articles

Check the published articles of the bioinformatics group about cancer.

AI-guided identification of risk variants for adrenocortical tumors in TP53 p.R337H carrier children: a genetic association study. Figueiredo, et al., 2024. The Lancet Regional Health – Americas, 2024, 38, 100863.
Comprehensive Characterization of the Regulatory Landscape of Adrenocortical Carcinoma: Novel Transcription Factors and Targets Associated with Prognosis. Muzzi, et al., 2022. Cancers (Basel). 2022 Oct 27; 14(21):5279.
Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes. Muzzi, et al., 2021. Frontiers in Endocrinology (Lausanne). 2021 Jun 14; 12:672319.
Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility. Pinto, et al., 2024. Human Genetics and Genomics (HGG) Advances. 2024 Jan 11; 5(1):100244.
XAF1 as a modifier of p53 function and cancer susceptibility. Pinto, et al., 2020. Science Advances, 24; 6(26):eaba3231.
Identification of epigenetic regulatory networks associated with the basal-like breast cancer subtype. Okano LM, et al. Cancer Research, 2023), 83 (7 Supplement), 6544.
Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients. Almohaywi M, et al. International Journal of Molecular Sciences. 2023 Aug 22; 24(17):13046.
Systems biology network reveals the correlation between COX-2 expression and Ch 7q copy number alterations in Ch 11q-deleted pediatric neuroblastoma tumors. Gradowski Farias da Costa do Nascimento T, et al. Genes Cancer. 2022 Dec 2; 13:60-71.
MiR-150-5p Overexpression in Triple-Negative Breast Cancer Contributes to the In Vitro Aggressiveness of This Breast Cancer Subtype. Sugita BM, et al. Cancers (Basel). 2022 Apr 26; 14(9):2156.
QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation. Bhattarai S, et al. International Journal of Molecular Sciences. 2021 Oct 26; 22(21):11548.
Integrated analysis of label-free quantitative proteomics and bioinformatics reveal insights into signaling pathways in male breast cancer. Gomig THB, et al. Genetics and Molecular Biology. 2021 Mar 1; 44(1):e20190410.
High-throughput mass spectrometry and bioinformatics analysis of breast cancer proteomic data. Gomig THB, et al. Data in Brief. 2019 Jun 10; 25:104125
Identification of epigenetic regulatory networks associated with the basal-like breast cancer subtype. Larissa Miyuki Okano; Alexandre Luiz Azevedo; Tamyres Mingorance Carvalho; Fernanda Brandão Berti; Luciane Regina Cavalli. Cancer Res (2023) 83 (7_Supplement): 6544. doi.org/10.1158/1538-7445.AM2023-6544
Relative telomere length analysis in breast cancer patients with TP53 p.R337H and XAF1 p.E134* germline variants Larissa M. Okano; Stéfanne M. Bortoletto; Mariana Paraizo; Aline S. Fonseca; Bonald C. Figueiredo; Enilze M F. Ribeiro; Ariana Centa , Luciane R.Cavalli. Cancer Res (2024) 84 (6_Supplement): 1643. doi.org/10.1158/1538-7445.AM2024-1643.
Lobo-Alves SC, Alves de Oliveira L, Canalli Kretzschmar G, Valengo AE, Rosati R (2024). Long noncoding RNA expression in acute lymphoblastic leukemia: A systematic review . CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, ISSN: 1040-8428
Oliveira LA, Kretzschmar GC, Lobo-Alves SC, Prezia GNB, Bispo S, Rosati R. The widespread misuse of StringTie's gene identifier tags as de facto gene symbols does not allow consistent gene identification in published research. Gene. 2025 Jun 20;954:149440. doi: 10.1016/j.gene.2025.149440.

Bioinformatics: Genomic and Metagenomic of Microorganisms

Microbiome - Metabarcoding and Metagenomics
Genomic analysis of antimicrobial resistant in bacteria, fungi and communities

The project

With the declining costs of next-generation genomic sequencing (NGS), the team at Pelé Pequeno Príncipe Research Institute’s Microbiology Laboratory has increasingly used this technique to complement its research projects.

Currently, the team employs both short- and long-read genomic sequencing methodologies, utilizing the NextSeq platform from Illumina® and MinION from Oxford®, respectively. Thus, the different research projects have generated a significant amount of data that needs to be analyzed with bioinformatics tools and a large computing structure.

Objective

The objective of the rare diseases Big Data project is to understand the genetic background behind the pathophysiological mechanisms of rare diseases, which will contribute to the development of new treatments.

Research projects that use NGS involve amplicon genomics of bacteria and fungi, utilizing markers such as 16S rRNA and ITS are used. They also address bacterial and fungal genomics, such as Klebsiella pneumoniae and Candida tropicalis. Finally, they involve shotgun metagenomics of hospital sewage samples.

Currently, this research group carries out projects in partnership with the Paraná Sanitation Company (Sanepar, abbreviation in Portuguese) and the Federal University of Paraná (UFPR, also in Portuguese), both in Brazil.

About the studies developed by the group

One of the group's studies focuses on intestinal microbiota in hematological and rare diseases. Acute Lymphoblastic Leukemia (ALL) is characterized by clonal proliferation and accumulation of lymphoblasts in the bone marrow and extramedullary tissues, associated with errors in cellular maturation. The gut microbiota plays a crucial role in modulating the immune system and protecting against pathogens; however, intestinal dysbiosis can lead to severe complications and increase the risk of bloodstream infections.

This project aims to evaluate the effects of chemotherapy on the gut microbiota of pediatric patients with ALL, as well as the relationship between these changes and clinical responses to treatment, with the goal of identifying potential early markers of therapeutic response. Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect in one of the enzyme subunits of the NADPH oxidase complex. This study seeks to characterize the gut microbiota of a child with CGD who is on continuous antimicrobial therapy, and to compare it with the microbiota of his family members.

Another study conducted by our group involves genomic analysis of antibiotic-resistant bacteria. In this research, databases such as NCBI and various bioinformatics tools were used to analyze large datasets and extract relevant biological information. One of the important pathogens evaluated is Klebsiella pneumoniae, which is commonly associated with opportunistic nosocomial infections in hospitalized patients. This bacterium often carries antimicrobial resistance genes that are frequently inserted into mobile genetic elements, allowing transfer among different bacteria.

Objectives

The objective of the research project on intestinal microbiota in hematological and rare diseases is to use shotgun and metabarcode sequencing approaches, such as the 16S rRNA gene and the ITS region, to identify changes in microbiota composition and establish possible biomarker organisms.

The objective of the genomic analysis of antibiotic-resistant bacteria project is to develop in silico analyses using genomic information from organisms of clinical interest in the One Health context. The Pelé Pequeno Príncipe Research Institute group used databases, such as NCBI and bioinformatics tools, to analyze large datasets and extract relevant biological information.

Team

Meet the team behind this research group.

Líbera Maria Dalla Costa – Pelé Pequeno Príncipe Research Institute (lead researcher)
Dany Alberto Mesa Fiaga – Pelé Pequeno Príncipe Research Institute
Damaris Krul – Pelé Pequeno Príncipe Research Institute
Danieli Conte - Pelé Pequeno Príncipe Research Institute
Lorena Bavia - Pelé Pequeno Príncipe Research Institute
Regiane Nogueira Spalanzani - Pelé Pequeno Príncipe Research Institute
Thaís Muniz Vasconcelos - Pelé Pequeno Príncipe Research Institute
Luiza Souza Rodrigues - Pelé Pequeno Príncipe Research Institute
Adriele Celine Siqueira - Pelé Pequeno Príncipe Research Institute

Published articles

Check the published articles of the bioinformatics group about microbiota and genomics.

High-risk clones of carbapenem resistant Klebsiella pneumoniae recovered from pediatric patients in Southern Brazil. Krul D, Rodrigues LS, Siqueira AC et al. Brazilian Journal of Microbiology, 2024, 1437–1443.
Outbreak of vancomycin-resistant Enterococcus faecium ST1133 in pediatric patients with acute lymphoblastic leukemia from southern Brazil. Vasconcelos TM, Mesa D, Rodrigues LS, Santos EM, Krul D, Siqueira AC, Abreu RBV, Motta, FA, Conte D, Dalla-Costa LM. Journal of Global Antimicrobial Resistance, 2024, 36, 41–44.
Analysis of Clostridioides difficile Infection in Children with Diarrhea in Two Hospitals in Southern Brazil. Maestri AC, Mesa D, Vasconcelos TM et al. Current Microbiology, 2023, 80, 390.
Lower airway microbiota and decreasing lung function in young Brazilian cystic fibrosis patients with pulmonary Staphylococcus and Pseudomonas infection. Kussek P, Mesa D, Vasconcelos TM, Rodrigues LS, Krul D, Ibañez H et al. PLoS ONE. 2022, 17(8): e0273453
Novel Insights into blaGES Mobilome Reveal Extensive Genetic Variation in Hospital Effluents. Conte D, Mesa D, Jové T, Zamparette CP, Sincero TCM, Palmeiro JK, Dalla-Costa LM. Microbiology Spectrum. 2022, 10:e02469-21.
First Genome Sequences of Two Multidrug-Resistant Candida haemulonii var. vulnera Isolates From Pediatric Patients With Candidemia. Rodrigues LS, Gazara RK, Passarelli-Araujo H, Valengo AE, Pontes PVM, Nunes-da-Fonseca R, de Souza RF, Venancio TM, Dalla-Costa LM. Frontiers in Microbiology. 2020 Jul, 11.
Comparative genomics of IncQ1 plasmids carrying blaGES variants from clinical and environmental sources in Brazil. Conte D, Mesa D, Krul D, Bail L, Ito CAS, Palmeiro JK, Dalla-Costa LM. Infect Genet Evol. 2024 Sep;123:105644.
Antimicrobial resistance in Aeromonas species isolated from aquatic environments in Brazil. Conte D, Palmeiro JK, Bavaroski AA, Rodrigues LS, Cardozo D, Tomaz AP, Camargo JO, Dalla-Costa LM. J Appl Microbiol. 2021 Jul;131(1):169-181.

Bioinformatics: Rare diseases

Exome/genome/transcriptome analysis of children and their relatives with rare diseases

The project

About rare diseases

Rare diseases affect 65 out of 100,000 inhabitants, according to the World Health Organization (WHO). This represents between 6% and 8% of the world population. There are approximately 7,000 rare diseases identified to date, with 50% of these conditions manifesting clinically during childhood. Notably, 80% of rare diseases have a genetic origin. Less than 5% of rare diseases have an approved specific treatment.

Objective

Team

Meet the team behind this research group.

Carolina Cardoso de Melo Prando – Pelé Pequeno Príncipe Research Institute (lead researcher)
Saloê Bispo Poubel – Pelé Pequeno Príncipe Research Institute
Laire S. Ferreira – Pelé Pequeno Príncipe Research Institute
Luiza S. Mattos – Pelé Pequeno Príncipe Research Institute
Eliana D. Girardello – Pelé Pequeno Príncipe Research Institute

Published articles

Check the published articles of the bioinformatics group about rare diseases.