168 results on '"César Paz-y-Miño"'
Search Results
2. Cytogenetic and genomic analysis of a patient with turner syndrome and t(2;12): a case report
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Paola E. Leone, Verónica Yumiceba, Ariana Jijón-Vergara, Andy Pérez-Villa, Isaac Armendáriz-Castillo, Jennyfer M. García-Cárdenas, Santiago Guerrero, Patricia Guevara-Ramírez, Andrés López-Cortés, Ana K. Zambrano, Jesús M. Hernández-Rivas, Juan Luis García, and César Paz-y-Miño
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Turner syndrome ,Reciprocal translocation ,Cytogenetics ,Genetic mapping arrays ,FISH ,Genetics ,QH426-470 - Abstract
Abstract Background Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool. Conclusion To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.
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- 2020
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3. Tracing the genetic history of the ‘Cañaris’ from Ecuador and Peru using uniparental DNA markers
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José R. Sandoval, Daniela R. Lacerda, Marilza M. S. Jota, Paulo Robles-Ruiz, Pierina Danos, César Paz-y-Miño, Spencer Wells, Fabrício R. Santos, and Ricardo Fujita
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Population genetics ,Cañaris ,SNP ,Short tandem repeats ,Y chromosome ,Mitochondrial DNA ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of Tawantinsuyu, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris–Inkawasi communities of a village, a former Inka camp, which persists until the present day. This scenario could explain these toponyms, but it is still controversial. To clarify this historical question, the study presented here focused on the inference of the genetic relationship between ‘Cañaris’ populations, particularly of Cañar and Ferreñafe, compared to other highland populations. We analysed native patrilineal Y chromosome haplotypes composed of 15 short tandem repeats, a set of SNPs, and maternal mitochondrial DNA haplotypes of control region sequences. Results After the genetic comparisons of local populations—three from Ecuador and seven from Peru—, Y chromosome analyses (n = 376) indicated that individuals from the Cañar region do not share Y haplotypes with the Kañaris, or even with those of the Inkawasi. However, some Y haplotypes of Ecuadorian ‘Cañaris’ were associated with haplotypes of the Peruvian populations of Cajamarca, Chivay (Arequipa), Cusco and Lake Titicaca, an observation that is congruent with colonial records. Within the Kañaris and Inkawasi communities there are at least five clans in which several individuals share haplotypes, indicating that they have recent common ancestors. Despite their relative isolation, most individuals of both communities are related to those of the Cajamarca and Chachapoyas in Peru, consistent with the spoken Quechua and their geographic proximity. With respect to mitochondrial DNA haplotypes (n = 379), with the exception of a shared haplotype of the D1 lineage between the Cañar and Kañaris, there are no genetic affinities. Conclusion Although there is no close genetic relationship between the Peruvian Kañaris (including Inkawasi) and Ecuadorian Cañar populations, our results showed some congruence with historical records.
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- 2020
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4. Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report
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Andrés López-Cortés, Ana Karina Zambrano, Patricia Guevara-Ramírez, Byron Albuja Echeverría, Santiago Guerrero, Eliana Cabascango, Andy Pérez-Villa, Isaac Armendáriz-Castillo, Jennyfer M. García-Cárdenas, Verónica Yumiceba, Gabriela Pérez-M, Paola E. Leone, and César Paz-y-Miño
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CIPA ,Native American ,Ecuadorian ,NTRK1 ,Genomics analysis ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Case presentation Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. Conclusions This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.
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- 2020
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5. A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report
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Jennyfer M. García-Cárdenas, Ana Karina Zambrano, Patricia Guevara-Ramírez, Santiago Guerrero, Gabriel Runruil, Andrés López-Cortés, Jorge P. Torres-Yaguana, Isaac Armendáriz-Castillo, Andy Pérez-Villa, Verónica Yumiceba, Paola E. Leone, and César Paz-y-Miño
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Pediatric anaplastic astrocytoma ,High-grade gliomas ,TP53 ,Li-Fraumeni syndrome ,Medicine - Abstract
Abstract Background Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment. Case presentation Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma. Conclusions Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.
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- 2020
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6. Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review
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César Paz-y-Miño, Ana Proaño, Stella D. Verdezoto, Juan Luis García, Jesús María Hernández-Rivas, and Paola E. Leone
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46,XX,r(4)(p16.3q35.2) ,Ring chromosome 4 ,Mosaic ,inv dup del rearrangement ,FISH ,Mapping array ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical “ring syndrome.”
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- 2019
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7. Ring chromosome 15 – cytogenetics and mapping arrays: a case report and review of the literature
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César Paz-y-Miño, Jaime Guevara-Aguirre, Ariane Paz-y-Miño, Francesca Velarde, Isaac Armendáriz-Castillo, Verónica Yumiceba, Jesús María Hernández, Juan Luis García, and Paola E. Leone
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Ring 15 ,Mapping arrays ,Cytogenetics ,Ring review ,Medicine - Abstract
Abstract Background Ring chromosome 15 has been associated in previous studies with different clinical characteristic such as cardiac problems, digit and musculoskeletal abnormalities, and mental and motor problems among others. Only 97 clinical cases of ring chromosome 15 syndrome have been reported since 1966 and a common phenotype for these patients has not been established. Case presentation The present case report describes a 15-month-old girl from the Amazon region of Ecuador, of Mestizo ancestry, who after cytogenetic tests showed a 46,XX,r(15) karyotype in more than 70% of metaphases observed. Her parents were healthy and non-related. The pregnancy was complicated and was positive for intrauterine growth retardation. Her birth weight was 1950 g, her length was 43.5 cm, and she had a head circumference of 29.3. In addition to postnatal growth delay, she had scant frontal hair, small eyes, hypertelorism, low-set of ears, flattened nasal bridge, anteverted nostrils, down-turned mouth, three café au lait spots, and delayed dentition. Conclusions Despite the frequency of some phenotypes expressed in the different clinical cases reviewed and the present case, a common phenotype for patients with ring 15 could not be determined and it is restricted to the region of the chromosome lost during the ring formation.
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- 2018
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8. In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19
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Andrés López-Cortés, Patricia Guevara-Ramírez, Nikolaos C. Kyriakidis, Carlos Barba-Ostria, Ángela León Cáceres, Santiago Guerrero, Esteban Ortiz-Prado, Cristian R. Munteanu, Eduardo Tejera, Doménica Cevallos-Robalino, Ana María Gómez-Jaramillo, Katherine Simbaña-Rivera, Adriana Granizo-Martínez, Gabriela Pérez-M, Silvana Moreno, Jennyfer M. García-Cárdenas, Ana Karina Zambrano, Yunierkis Pérez-Castillo, Alejandro Cabrera-Andrade, Lourdes Puig San Andrés, Carolina Proaño-Castro, Jhommara Bautista, Andreina Quevedo, Nelson Varela, Luis Abel Quiñones, and César Paz-y-Miño
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COVID-19 ,immune system ,single-cell RNA sequencing ,artificial neural networks ,drug repurposing ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19.Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics.Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.
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- 2021
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9. Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis
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Verónica Yumiceba, Andrés López-Cortés, Andy Pérez-Villa, Iván Yumiseba, Santiago Guerrero, Jennyfer M. García-Cárdenas, Isaac Armendáriz-Castillo, Patricia Guevara-Ramírez, Paola E. Leone, Ana Karina Zambrano, and César Paz-y-Miño
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polycystic ovary syndrome (PCOS) ,endometrial cancer (EC) ,ovarian cancer (OC) ,breast cancer (BC) ,pharmacogenomics ,bioinformatic ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types. PTEN had the highest number of mutations in EC, TP53, in OC, and FSHR, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion, in silico analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.
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- 2020
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10. Multi‐institutional experience of genetic diagnosis in Ecuador: National registry of chromosome alterations and polymorphisms
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César Paz‐y‐Miño, Verónica Yumiceba, Germania Moreta, Rosario Paredes, Mónica Ruiz, Ligia Ocampo, Arianne Llamos Paneque, Catalina Ochoa Pérez, Juan Carlos Ruiz‐Cabezas, Jenny Álvarez Vidal, Idarmis Jiménez Torres, Ramón Vargas‐Vera, Fernando Cruz, Víctor Hugo Guapi N, Martha Montalván, Sara Meneses Álvarez, Maribel Garzón Castro, Elizabeth Lamar Segura, María Augusta Recalde Báez, María Elena Naranjo, Nina Tambaco Jijón, María Sinche, Pedro Licuy, Ramiro Burgos, Fabián Porras‐Borja, Gabriela Echeverría‐Garcés, Andy Pérez‐Villa, Isaac Armendáriz‐Castillo, Jennyfer M. García‐Cárdenas, Santiago Guerrero, Patricia Guevara‐Ramírez, Andrés López‐Cortés, Ana Karina Zambrano, and Paola E. Leone
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chromosome alterations ,chromosome polymorphisms ,cytogenetics ,genetic testing ,Genetics ,QH426-470 - Abstract
Abstract Background Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador. Methods Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open‐access national registry of chromosome alterations and polymorphisms. Results Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes. Conclusion The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing.
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- 2020
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11. Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis
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Eduardo Tejera, Maykel Cruz-Monteagudo, Germán Burgos, María-Eugenia Sánchez, Aminael Sánchez-Rodríguez, Yunierkis Pérez-Castillo, Fernanda Borges, Maria Natália Dias Soeiro Cordeiro, César Paz-y-Miño, and Irene Rebelo
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Consensus analysis ,Gene periodization ,Preeclampsia ,Communality analysis ,Microarray analysis ,Pathogenesis ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. Methods We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. Results The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. Conclusion Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.
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- 2017
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12. Post-transcriptional Regulation of Colorectal Cancer: A Focus on RNA-Binding Proteins
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Jennyfer M. García-Cárdenas, Santiago Guerrero, Andrés López-Cortés, Isaac Armendáriz-Castillo, Patricia Guevara-Ramírez, Andy Pérez-Villa, Verónica Yumiceba, Ana Karina Zambrano, Paola E. Leone, and César Paz-y-Miño
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colorectal cancer ,RBPs ,post-transcriptional regulation ,oncogene ,tumor suppressor ,Biology (General) ,QH301-705.5 - Abstract
Colorectal cancer (CRC) is a major health problem with an estimated 1. 8 million new cases worldwide. To date, most CRC studies have focused on DNA-related aberrations, leaving post-transcriptional processes under-studied. However, post-transcriptional alterations have been shown to play a significant part in the maintenance of cancer features. RNA binding proteins (RBPs) are uprising as critical regulators of every cancer hallmark, yet little is known regarding the underlying mechanisms and key downstream oncogenic targets. Currently, more than a thousand RBPs have been discovered in humans and only a few have been implicated in the carcinogenic process and even much less in CRC. Identification of cancer-related RBPs is of great interest to better understand CRC biology and potentially unveil new targets for cancer therapy and prognostic biomarkers. In this work, we reviewed all RBPs which have a role in CRC, including their control by microRNAs, xenograft studies and their clinical implications.
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- 2019
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13. A quick guide for using Microsoft OneNote as an electronic laboratory notebook.
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Santiago Guerrero, Andrés López-Cortés, Jennyfer M García-Cárdenas, Pablo Saa, Alberto Indacochea, Isaac Armendáriz-Castillo, Ana Karina Zambrano, Verónica Yumiceba, Andy Pérez-Villa, Patricia Guevara-Ramírez, Oswaldo Moscoso-Zea, Joel Paredes, Paola E Leone, and César Paz-Y-Miño
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Biology (General) ,QH301-705.5 - Abstract
Scientific data recording and reporting systems are of a great interest for endorsing reproducibility and transparency practices among the scientific community. Current research generates large datasets that can no longer be documented using paper lab notebooks (PLNs). In this regard, electronic laboratory notebooks (ELNs) could be a promising solution to replace PLNs and promote scientific reproducibility and transparency. We previously analyzed five ELNs and performed two survey-based studies to implement an ELN in a biomedical research institute. Among the ELNs tested, we found that Microsoft OneNote presents numerous features related to ELN best functionalities. In addition, both surveyed groups preferred OneNote over a scientifically designed ELN (PerkinElmer Elements). However, OneNote remains a general note-taking application and has not been designed for scientific purposes. We therefore provide a quick guide to adapt OneNote to an ELN workflow that can also be adjusted to other nonscientific ELNs.
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- 2019
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14. Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis
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Alejandro Cabrera-Andrade, Andrés López-Cortés, Gabriela Jaramillo-Koupermann, César Paz-y-Miño, Yunierkis Pérez-Castillo, Cristian R. Munteanu, Humbert González-Díaz, Alejandro Pazos, and Eduardo Tejera
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gene prioritization ,osteosarcoma ,communality analysis ,pathogenesis ,early recognition ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein−protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.
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- 2020
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15. Understanding Celiac Disease From Genetics to the Future Diagnostic Strategies
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Carolina Salazar, Jennyfer M García-Cárdenas, and César Paz-y-Miño
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Celiac disease (CD) is an autoimmune disorder characterized by the permanent inflammation of the small bowel, triggered by the ingestion of gluten. It is associated with a number of symptoms, the most common being gastrointestinal. The prevalence of this illness worldwide is 1%. One of the main problems of CD is its difficulty to be diagnosed due to the various presentations of the disease. Besides, in many cases, CD is asymptomatic. Celiac disease is a multifactorial disease, HLA-DQ2 and HLA-DQ8 haplotypes are predisposition factors. Nowadays, molecular markers are being studied as diagnostic tools. In this review, we explore CD from its basic concept, manifestations, types, current and future methods of diagnosis, and associated disorders. Before addressing the therapeutic approaches, we also provide a brief overview of CD genetics and treatment.
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- 2017
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16. Analysis and Implementation of an Electronic Laboratory Notebook in a Biomedical Research Institute.
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Santiago Guerrero, Gwendal Dujardin, Alejandro Cabrera-Andrade, César Paz-Y-Miño, Alberto Indacochea, Marta Inglés-Ferrándiz, Hima Priyanka Nadimpalli, Nicola Collu, Yann Dublanche, Ismael De Mingo, and David Camargo
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Medicine ,Science - Abstract
Electronic laboratory notebooks (ELNs) will probably replace paper laboratory notebooks (PLNs) in academic research due to their advantages in data recording, sharing and security. Despite several reports describing technical characteristics of ELNs and their advantages over PLNs, no study has directly tested ELN performance among researchers. In addition, the usage of tablet-based devices or wearable technology as ELN complements has never been explored in the field. To implement an ELN in our biomedical research institute, here we first present a technical comparison of six ELNs using 42 parameters. Based on this, we chose two ELNs, which were tested by 28 scientists for a 3-month period and by 80 students via hands-on practical exercises. Second, we provide two survey-based studies aimed to compare these two ELNs (PerkinElmer Elements and Microsoft OneNote) and to analyze the use of tablet-based devices. We finally explore the advantages of using wearable technology as ELNs tools. Among the ELNs tested, we found that OneNote presents almost all parameters evaluated (39/42) and both surveyed groups preferred OneNote as an ELN solution. In addition, 80% of the surveyed scientists reported that tablet-based devices improved the use of ELNs in different respects. We also describe the advantages of using OneNote application for Apple Watch as an ELN wearable complement. This work defines essential features of ELNs that could be used to improve ELN implementation and software development.
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- 2016
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17. Relationship of an hRAD54 gene polymorphism (2290 C/T) in an Ecuadorian population with chronic myelogenous leukemia
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César Paz-y-Miño, Andrés López-Cortés, María José Muñoz, Bernardo Castro, Alejandro Cabrera, and María Eugenia Sánchez
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cancer ,leukemia ,CML ,ALL ,hRAD54 ,2290 C/T polymorphism ,Genetics ,QH426-470 - Abstract
The hRAD54 gene is a key member of the RAD52 epistasis group involved in repair of double-strand breaks (DSB) by homologous recombination (HR). Thus, alterations of the normal function of these genes could generate genetic instability, shifting the normal process of the cell cycle, leading the cells to develop into cancer. In this work we analyzed exon 18 of the hRAD54 gene, which has been previously reported by our group to carry a silent polymorphism, 2290 C/T (Ala730Ala), associated to meningiomas. We performed a PCR-SSCP method to detect the polymorphism in 239 samples including leukemia and normal control population. The results revealed that the 2290 C/T polymorphism has frequencies of 0.1 for the leukemia and 0.1 for the control group. These frequencies show no statistical differences. Additionally, we dissected the leukemia group in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) to evaluate the polymorphism. The frequencies found in these subgroups were 0.14 for CML and 0.05 for ALL. We found statistically significant differences between CML patients and the control group (p < 0.05) but we did not find significant differences between ALL and the control group (p > 0.05). These results suggest a possible link between the 2290 C/T polymorphism of the hRAD54 gene and CML.
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- 2010
18. Evaluation of DNA damage in an Ecuadorian population exposed to glyphosate
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César Paz-y-Miño, María Eugenia Sánchez, Melissa Arévalo, María José Muñoz, Tania Witte, Gabriela Oleas De-la-Carrera, and Paola E. Leone
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comet assay ,DNA damage ,Ecuador ,genotoxicity ,glyphosate ,Genetics ,QH426-470 - Abstract
We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. A total of 24 exposed and 21 unexposed control individuals were investigated using the comet assay. The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 µm) compared to the control group (comet length = 25.94 µm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals.
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- 2007
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19. Use, knowledge, attitudes and practices of formal and alternative medicine related to Covid-19 in the Ecuadorian population
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César Paz-y-Miño and Paola E. Leone
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Infectious Diseases ,Epidemiology ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
The Covid-19 pandemic revealed a complex health problem for people and national health systems. Faced with the initial ignorance of the behavior of the SARS-COV-2 virus in populations, people turned to relief and alternative medicines. In Ecuador, the use of traditional or western medicine and the systematic approach of people to conventional medicine are evident realities. Our work aimed to assess the knowledge, attitudes and practices regarding Covid-19 and the use of formal and traditional medicine to treat the disease or contagion. An open, personal and confidential survey was carried out, with 158 questions on general data, ethnicity, health status, covid-19 tests, use of self-medication, use of medicinal plants or other chemical products, and use of antibiotics or antiparasitics, among other data. In the control of the patients, six months after finishing the survey, they were asked about the acceptance of the vaccine and the decision to be vaccinated or not. The results in 3,000 persons (50% female and 50% male) show frequent use of alternative or traditional medicine, even in health personnel or university studies. The study's conclusions reflect that people choose any of the therapies they have access to and even mix traditional treatments with traditional ones that are unproven or toxic. Keywords: knowledge, attitudes, practices, covid-19, formal medicine, traditional medicine
- Published
- 2022
20. Progresos genéticos y genómicos en el cáncer de mama
- Author
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César Paz-y-Miño
- Subjects
General Medicine - Abstract
Se presenta una revisión sobre el estado del conocimiento de la genética y la genómica del cáncer de mama. Se hace referencia a estudios globales sobre genes de predisposición a este tipo de cáncer, así como genes de apoyo al diagnóstico y tratamiento. Adicionalmente se nombran algunos genes útiles en el trabajo clínico y en el manejo del cáncer de mama.
- Published
- 2022
21. Rare pathology derived from a ring chromosome 15. Clinical, genomic and protein interactome of genes associated with the phenotype
- Author
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César Paz-y-Miño, Camila Medranda, Alejandra Loaiza, Mishell Ponce, and Paola E. Leone
- Subjects
Infectious Diseases ,Epidemiology ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
The case of a 4-year-two-month-old female patient is presented, who consulted for a special phenotype: psychomotor retardation, short stature, microcephaly, large and low-set ears, small forehead, prominent brow ridges, labial commissure open, ocular hypertelorism, short neck, mammary hypertelorism and pectus excavatum. The objective of this study is to analyze a patient with unusual phenotypic traits, through physical examination, comparative analysis with other cases, and genetic studies. The cytogenetic study revealed a mosaic karyotype, mos 46,XX,r(15)(q26.3)/46,XX with the presence of the ring in 83%. The genetic mapping array study identified the loss of 3.5 Mb in 15q26.3. Among the genes lost in the terminal region of 15q, an interaction between their protein products was evidenced according to the STRING analysis. This is the second case of a ring chromosome 15 reported in Ecuador. And it would be the 101st in the world since 1966. The special phenotype of these individuals is related to the amount of genetic material lost. The genes involved in the formation of the ring, as well as the proteins that determine these genes and the relationships in different cellular pathways, are analyzed in silico in order to understand the pathophysiology of this disorder. Its diagnosis is mostly postnatal, so the clinical approach differs individually according to the symptoms and signs that appear.
- Published
- 2022
22. Genetics of Multiple Myeloma in Latin America
- Author
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Paola E. Leone, Virginia Abello, Cristian Gerardo Alvarado, Jose Alvarez, Gabriel Borelli, Maria Elena Del Rocio Buenaño, Wendy Cabrera, Fernando Camacho, Milton Rafael Carranza Orellana, Denisse Castro, Francisco Cevallos, Natalia Córdova, Marcos Di Stefano, Víctor Hugo Espín, Ramiro Espinoza, Aida Falcon de Vargas, Raul Gabus, Xavier García León, Ivonne Guerrero Alva, Andrés F. Leone, Monica Maria Monsalve Moreno, Rodrigo Motta, Ligia Enit Ocampo Rojas, Julieta Panero, César Paz-y-Miño, Estela Pedrazzini, Camila Peña, Juvenal Ríos, Eloísa Riva, Iris Rivera, Aurora Romero Coronel, Juan Carlos Ruiz Cabezas, Irma Slavutsky, Carmen Graciela Stanganelli, Flavia Stella, and Víctor Villarroel
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
23. INFECTION DYNAMICS OF BATRACHOCHYTRIUM DENDROBATIDIS IN TWO FROG SPECIES INHABITING QUITO'S METROPOLITAN GUANGÜILTAGUA PARK, ECUADOR
- Author
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G. Burgos, Alexander Genoy-Puerto, Alejandro Cabrera-Andrade, Andrés Merino-Viteri, David A. Narváez-Narváez, and César Paz-y-Miño
- Subjects
Batrachochytrium ,Amphibian ,education.field_of_study ,Ecology ,biology ,Population ,Prevalence ,Zoology ,biology.organism_classification ,Arthropod mouthparts ,Gastrotheca riobambae ,Chytridiomycota ,Mycoses ,biology.animal ,Reproductive biology ,Pristimantis unistrigatus ,Animals ,Ecuador ,Chytridiomycosis ,Anura ,education ,Ecology, Evolution, Behavior and Systematics - Abstract
Batrachochytrium dendrobatidis (Bd) infection is one of the principal causes of amphibian declines worldwide. The presence of Bd has been determined in Gastrotheca riobambae tadpoles that inhabit ponds in Quito's Metropolitan Guangüiltagua Park, Ecuador. This study sought to determine whether these tadpoles are infected and to determine the presence of chytridiomycosis in another frog species, Pristimantis unistrigatus, which also inhabits the park and has different reproductive biology and distinct behavioral habits. We used end-point and real-time PCR techniques to detect and quantify Bd infection. At 1 yr, samples were taken from the skin of P. unistrigatus using swabs and were also taken from the mouthparts of G. riobambae tadpoles. It was found that the two species were infected with a Bd prevalence of 39% (53/135) in G. riobambae tadpoles and 15% (57/382) in P. unistrigatus frogs. The two types of samples (tissue and swabs) from mouthparts showed differences in the zoospores per microliter loads (x̄=1,376.7±3,450.2 vs. x̄=285.0±652.3). Moreover, a correlation (r2=0.621) was discovered between the monthly mean maximum temperature of the pond with disease prevalence in G. riobambae tadpoles. Infection levels in the P. unistrigatus population varied significantly over time, and distance to the pond was a determinant factor for infection intensity.
- Published
- 2021
24. Allele frequency data for 15 autosomal strs and ancestral proportions using aims-indels in the shuar ethnic group from Ecuador
- Author
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Santiago Guerrero, Paola E. Leone, Verónica Yumiceba, Jennyfer M. García-Cárdenas, Andy Pérez-Villa, D. Maldonado-Oyervide, Isaac Armendáriz-Castillo, O. Astudillo-González, Patricia Guevara-Ramírez, César Paz-y-Miño, Andrés López-Cortés, and Ana Karina Zambrano
- Subjects
Genetic diversity ,education.field_of_study ,Paternity Index ,010401 analytical chemistry ,Population ,Ethnic group ,Biology ,01 natural sciences ,0104 chemical sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Tandem repeat ,Evolutionary biology ,Polymorphism (computer science) ,Genetics ,030216 legal & forensic medicine ,Indel ,education ,Allele frequency - Abstract
The ethnic group Shuar is located in Ecuador. To identify their genetic composition, 46 ancestry-informative insertion deletion markers (AIM-INDELs) were used. Also, characterization of 15 tandem repeats (STRs) in the AmpFISTR Identifiler Kit were applied. Forensic parameters showed a matching probability of 0.1535, a power of discrimination of 0.8465, a polymorphism information content of 0.6584, probability of exclusion of 0.415 and a typical paternity index of 1.78. The Shuar are not influenced by admixture population events, being a Native American group 98.7%, along with a genetic diversity of 0.699346+/-0.356964.
- Published
- 2019
25. Genetic characterization of 12 STRs (Investigator® HDplex kit) in the Ecuadorian population
- Author
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Anibal Gaviria, Gisella Fiallos, César Paz-y-Miño, Lissett Boada, Cristina Rodríguez-Pólit, Carmen Gruezo, M. Vela, and Ana Karina Zambrano
- Subjects
Loss of heterozygosity ,Genetics ,education.field_of_study ,Population sample ,Population ,Microsatellite ,Genetic data ,Locus (genetics) ,Biology ,education ,Allele frequency ,Pathology and Forensic Medicine - Abstract
Allele frequencies, and genetic data for 12 autosomal Short Tandem Repeat (STRs) loci (D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D12S391, D18S51, D21S2055, and SE33 [ACTBP2]) using the Investigator® HDplex kit (QIAGEN) were obtained from 200 non-related individuals from the Ecuadorian mestizo population. Subjects included 100 men and 100 women, from the 24 provinces of Ecuador. Heterozygosity (Ho), power of discrimination (PD), power of exclusion (PE) and polymorphism information content (PIC) were estimated for the population sample. Locus SE33 had the highest values for power of discrimination (0.9372), polymorphism information content (0.9338), and power of exclusion (0.7852). The most informative STRs for the Ecuadorian population were SE33, D7S1517, D10S2325 and the least informative were D2S1360, D3S1744 and D6S474. The Investigator® HDplex makers have shown to be highly informative in the Ecuadorian population and are suitable as a powerful complementary tool in forensic analysis and complex kinship cases.
- Published
- 2019
26. Molecular variants associated with flavor perceptions and ancestral proportions of Ecuadorian populations
- Author
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Paola E. Leone, M.E. Dávalos, Ana Karina Zambrano, Jennyfer M. García-Cárdenas, Andy Pérez-Villa, Patricia Guevara-Ramírez, A.C. Cárdenas Figueroa, Andrés López-Cortés, Santiago Guerrero, Isaac Armendáriz-Castillo, Verónica Yumiceba, and César Paz-y-Miño
- Subjects
Genetics ,Taste ,education.field_of_study ,genetic structures ,media_common.quotation_subject ,Population ,food and beverages ,Single-nucleotide polymorphism ,Sweetness ,Biology ,Pathology and Forensic Medicine ,Perception ,Family history ,Allele ,education ,psychological phenomena and processes ,Flavor ,media_common - Abstract
The perception of taste is determined by several factors, including genetics, which at the same time is related with the diet and diseases in different populations. We aimed to identify the frequency of six single nucleotide polymorphisms (rs307355, rs35744813, rs713598, rs1726866, rs10246939 and rs11091046) involved in the perception of sweet, bitter and salty flavor in Ecuadorian mestizo population. It was found that the presence of the T allele of rs307355 and rs35744813 is associated with decreased ability of subjects to carry out specific discrimination of sweetness, this is particularly interesting given the correlation found (p = 0.0022) between sucrose perception and family history of cancer and diabetes. Furthermore, rs713598, rs1726866 and rs10246939 do not influence the ability to perceive the bitter taste. Concerning the perception of the salty taste, rs11091046 does influence the capacity of detecting it more easily. This theoretical knowledge of the genetic influence on taste perception can contribute to the understanding of eating habits and their impact on human health.
- Published
- 2019
27. Genetic variation of high-altitude Ecuadorian population using autosomal STR markers
- Author
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César Paz-y-Miño, Ana Karina Zambrano, Carmen Gruezo, Jennyfer M. García-Cárdenas, Andrés López-Cortés, Patricia Guevara-Ramírez, C. Rodríguez-Pollit, M. Vela, A. Gaviria, Verónica Yumiceba, Isaac Armendáriz-Castillo, Santiago Guerrero, Paola E. Leone, Gisella Fiallos, and Andy Pérez-Villa
- Subjects
education.field_of_study ,010401 analytical chemistry ,Population ,Str markers ,Effects of high altitude on humans ,01 natural sciences ,0104 chemical sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Geography ,Altitude ,Genetic distance ,Genetic variation ,Genetics ,030216 legal & forensic medicine ,education ,Demography - Abstract
Fifteen autosomal STRs were analyze in order to elucidate the differences between low and high land Ecuadorian population. Seven Ecuadorian geographic areas (Tisaleo-Mocha, Canar, Quito, Rocafuerte, Santa Rosa, Guayaquil and Lago Agrio) from different altitude were selected for the study. After the analysis, little genetic distances were observed between all cities, the more distant cities (FST = 0.02354) were Rocafuerte at an elevation of 17 m.a.s.l. and Quito at 2850 m.a.s.l. and the similar cities (FST = 0.00033) were Rocafuerte (17 m.a.s.l.) and Santa Rosa (10 m.a.s.l). In conclusion, there is not a great genetic distance in the 15 STRs reported in high and low land Ecuadorian population, therefore previously reported frequencies could been used in identification and paternity cases under analysis.
- Published
- 2019
28. Ancestral analysis of a Native American Ecuadorian family with congenital insensitivity to pain with anhidrosis
- Author
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Santiago Guerrero, Patricia Guevara-Ramírez, Verónica Yumiceba, Andy Pérez-Villa, Eliana Cabascango, Andrés López-Cortés, Paola E. Leone, Ana Karina Zambrano, B. Albuja Echeverría, Jennyfer M. García-Cárdenas, Isaac Armendáriz-Castillo, César Paz-y-Miño, and Gabriela Pérez-M
- Subjects
Genetics ,010401 analytical chemistry ,Ancestry-informative marker ,Consanguinity ,Biology ,medicine.disease ,01 natural sciences ,0104 chemical sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Congenital insensitivity to pain with anhidrosis ,Genetic variation ,Intellectual disability ,medicine ,Missense mutation ,030216 legal & forensic medicine ,Gene ,Allele frequency - Abstract
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by self-mutilating behavior, unexplained fever, inability to sweat and intellectual disability. CIPA pathogenesis is associated with genetic loss-of-function mutations of the NTRK1 gene, which is auto phosphorylated activating intracellular signaling transduction such as cell survival, growth and differentiation. CIPA occurs with an incidence of 1 in 125 million newborns, and only some hundreds of cases have been reported worldwide. Most of cases have been reported in Asian countries. Here, we estimate the ancestral proportions of a family with consanguinity background affected with CIPA, who carries the missense pathogenic mutations rs80356677 (Asp674Tyr) in the kinase domain of NTRK1 and rs324420 (Pro129Thr) in the FAAH gene. The ancestral proportion was calculated through 45 ancestry informative markers (AIMs) and the comparison was done through the Human Genome Diversity Project panel. The resulting allele frequencies in CIPA family indicate a prevalence of the Native American ancestral component with 87.9%, and minor proportion for the European (8.9%) and African (3%) components. In conclusion, the genetic variations expressing CIPA in a Native American Ecuadorian family could have been caused by the insertion of certain genetic characteristics, which have been passed down from common ancestors as consequence of migration towards South America.
- Published
- 2019
29. Genetic polymorphisms of 12 X-STRs in the Ecuadorian population
- Author
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Gisella Fiallos, Cristina Rodríguez-Pólit, Anibal Gaviria, M. Vela, Ana Karina Zambrano, Carmen Gruezo, César Paz-y-Miño, and Lissett Boada
- Subjects
Genetics ,education.field_of_study ,010401 analytical chemistry ,Population ,Locus (genetics) ,Biology ,Y chromosome ,01 natural sciences ,Hardy–Weinberg principle ,0104 chemical sciences ,Pathology and Forensic Medicine ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,030216 legal & forensic medicine ,education ,Allele frequency ,X chromosome - Abstract
The X-STR markers represent a powerful tool to complement the information provided by the autosomal and Y chromosome markers, particularly, in cases involving at least one woman. In the present study, allele frequencies, power of exclusion (PE), power of discrimination (PD) and polymorphism information content (PIC) were analyzed for 12 X chromosome loci. A total of 200 unrelated Ecuadorian individuals were selected for the population analysis. The data showed that DXS10135 locus had the highest power of discrimination value (PD = 0.9351), and polymorphism information content (PIC = 0.9313). The heterozygosity observed ranged from 0.9300 to 0.6400. The power of exclusion varied between 0.3417 to 0.8570 for DXS10135 and DXS8378 respectively. No significant departure from Hardy Weinberg equilibrium (HWE) was detected for any of the analyzed markers. The X-STR markers have demonstrated their potential to efficiently complement the analysis to solve complex kinship and forensic cases.
- Published
- 2019
30. X-STR decaplex study in the population of Imbabura-Ecuador
- Author
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Lissett Boada, César Paz-y-Miño, Cristina Rodríguez-Pólit, Anibal Gaviria, M. Vela, Ana Karina Zambrano, Carmen Gruezo, Gisella Fiallos, and Michelle Vaca-Pólit
- Subjects
Genetics ,education.field_of_study ,Daughter ,media_common.quotation_subject ,010401 analytical chemistry ,Population ,Str markers ,Population genetics ,Biology ,Y chromosome ,01 natural sciences ,0104 chemical sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Genetic distance ,030216 legal & forensic medicine ,education ,Allele frequency ,X chromosome ,media_common - Abstract
X chromosome STR markers are a useful tool in population genetics, they provide supplementary information for forensic and kinship analysis where autosomal and Y chromosome information is not enough. A total of 100 unrelated individuals from Imbabura-Ecuador were genotyped using the X-STR Decaplex system (DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08, and DXS7423). Allele frequencies and population parameters were calculated for each STR. The most informative marker was DXS6809 and the least informative was DXS7133. High discrimination power values were obtained (greater than 99.99%), as well as high mean exclusion chance in trios (mother / daughter / father) 0.9999948011 and duos (father/daughter) 0.9992880836. The genetic distance (FST) obtained comparing the Ecuadorian population and the Pichincha province population show low genetic distances. The data analyzed confirmed the potential of these 10 X-STRs.
- Published
- 2019
31. Pharmacogenomics, biomarker network, and allele frequencies in colorectal cancer
- Author
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César Paz-y-Miño, Néstor W. Soria, Jennyfer M. García-Cárdenas, Andrés López-Cortés, Patricia Guevara-Ramírez, Santiago Guerrero, Gabriela Jaramillo-Koupermann, Isaac Armendáriz-Castillo, Dámaris P. Intriago-Baldeón, Luis A. Quiñones, Paola E. Leone, Ángela León Cáceres, and Juan P Cayún
- Subjects
0301 basic medicine ,Colorectal cancer ,Antineoplastic Agents ,Single-nucleotide polymorphism ,Bioinformatics ,030226 pharmacology & pharmacy ,Causes of cancer ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Gene Regulatory Networks ,Allele frequency ,Therapeutic strategy ,Pharmacology ,business.industry ,medicine.disease ,Precision medicine ,Pharmacogenomics Biomarker ,030104 developmental biology ,Pharmacogenetics ,Pharmacogenomics ,Molecular Medicine ,Colorectal Neoplasms ,business - Abstract
Colorectal cancer is one of the leading causes of cancer death worldwide. Over the last decades, several studies have shown that tumor-related genomic alterations predict tumor prognosis, drug response, and toxicity. These observations have led to the development of several therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations which may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. We conduct a comprehensive review of the main pharmacogenomics biomarkers and genomic alterations affecting enzyme activity, transporter capacity, channels, and receptors; and therefore the new advances in CRC precision medicine to select the best therapeutic strategy in populations worldwide, with a focus on Latin America.
- Published
- 2019
32. Polimorfismos genéticos en pacientes con fisuras labio y/o palatinas no sindrómicos
- Author
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Paola E. Leone, Diana Cárdenas-Nieto, César Paz-y-Miño, and Maribel Forero-Castro
- Subjects
Genetics ,TBX1 ,MMP3 ,biology ,biology.protein ,Etiology ,ABCA4 ,Single-nucleotide polymorphism ,General Medicine ,PAX9 ,Phenotype ,Gene - Abstract
Dentro de los defectos congénitos más frecuentes se encuentran las fisuras labio y/o palatinas (FL/P), presentando una prevalencia de alrededor de 1:1.000 nacimientos vivos. El 70% de FL/P son de tipo no sindrómico, lo cual hace referencia a que se encuentran como un defecto aislado sin anomalías adicionales. Poseen una etiología compleja con un componente tanto ambiental como genético. Con el desarrollo de tecnologías de secuenciación del genoma humano se han identificado variantes polimórficas que pueden estar asociadas al fenotipo de FL/P y por tal motivo pueden contribuir a la etiología multifactorial de éstas. En esta revisión se describen las variantes comúnmente asociadas y su papel en la etiología de las FL/P. Los SNPs localizados en los genes IFR6, MSX1, VAX1, PAX9, CHD1, FGF1, GREM1 y WNT3 se han relacionado significativamente con la presencia de FL/P, y las variantes ubicadas en los genes APC, GSK3, DVL2, BMP4, ABCA4, BHMT, NTN1, TBX1, EPHA3, FAM49A, MGMT, MMP3, TIMP2 y NOG aunque se ha reportado su asociación con la presencia de las fisuras orofaciales aún no es clara su relación con dicho fenotipo. Es importante realizar estudios de identificación de variantes genéticas que involucren poblaciones específicas con el fin de poder comprender la etiología de las FL/P no sindrómicas.
- Published
- 2019
33. USO DE MICROSOFT ONENOTE COMO CUADERNO ELECTRÓNICO DE LABORATORIO
- Author
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Jennyfer M. García Cárdenas, Andrés López Cortés, Santiago Guerrero, Andy Pérez Villa, Patricia Guevara Ramírez, Verónica Yumiceba, Oswaldo Moscoso Zea, César Paz y Miño, Isaac Armendáriz Castillo, Paola E. Leone, Ana Karina Zambrano, Joel Paredes, and Pablo Saa
- Abstract
Los sistemas de registro y de reporte de datos son de gran interés, puesto que respaldan la reproducibilidad y transparencia científica. La investigación actual genera una gran cantidad de datos que ya no se pueden documentar utilizando cuadernos de laboratorio de papel (CLP). Los cuadernos electrónicos de laboratorio (CEL) podrían ser una solu-ción prometedora para reemplazar los CLP y promover la reproducibilidad científica y su transparencia. Anteriormente analizamos cinco CEL y realizamos dos encuestas para implementar un CEL en un instituto de investigación biomédica. Entre los CEL proba-dos, encontramos que Microsoft OneNote presenta numerosas características relacio-nadas con las mejores funcionalidades del CEL. Además, ambos grupos encuestados prefirieron OneNote sobre un CEL científico (Elements de PerkinElmer). Sin embargo, OneNote es una aplicación general para tomar notas que no ha sido diseñada para fi-nes científicos. Por lo tanto, en este trabajo proporcionamos varias pautas para adaptar OneNote a un flujo de trabajo experimental.
- Published
- 2019
34. A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report
- Author
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Andy Pérez-Villa, Andrés López-Cortés, Santiago Guerrero, Ana Karina Zambrano, Paola E. Leone, Patricia Guevara-Ramírez, Jorge P. Torres-Yaguana, Isaac Armendáriz-Castillo, Gabriel Runruil, Jennyfer M. García-Cárdenas, Verónica Yumiceba, and César Paz-y-Miño
- Subjects
Oncology ,medicine.medical_specialty ,Adolescent ,Cabozantinib ,Population ,lcsh:Medicine ,Case Report ,Astrocytoma ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,Humans ,Medicine ,TP53 ,Li-Fraumeni syndrome ,Family history ,Child ,education ,High-grade gliomas ,education.field_of_study ,business.industry ,lcsh:R ,High-Throughput Nucleotide Sequencing ,General Medicine ,medicine.disease ,Pediatric anaplastic astrocytoma ,FANCA ,Clinical trial ,chemistry ,Li–Fraumeni syndrome ,030220 oncology & carcinogenesis ,Female ,Ecuador ,Glioblastoma ,business ,Anaplastic astrocytoma - Abstract
Background Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment. Case presentation Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma. Conclusions Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.
- Published
- 2020
35. Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report
- Author
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Ana Karina Zambrano, Andy Pérez-Villa, Andrés López-Cortés, Jennyfer M. García-Cárdenas, Gabriela Pérez-M, Patricia Guevara-Ramírez, Eliana Cabascango, Byron Albuja Echeverría, Verónica Yumiceba, Santiago Guerrero, Isaac Armendáriz-Castillo, César Paz-y-Miño, and Paola E. Leone
- Subjects
0301 basic medicine ,Genetic Markers ,lcsh:Internal medicine ,lcsh:QH426-470 ,Pain Insensitivity, Congenital ,DNA Mutational Analysis ,Pain ,Case Report ,NTRK1 ,Disease ,Consanguinity ,03 medical and health sciences ,CIPA ,0302 clinical medicine ,Congenital insensitivity to pain with anhidrosis ,Intellectual disability ,Genetics ,medicine ,Missense mutation ,Ecuadorian ,Humans ,Protein Interaction Maps ,Anhidrosis ,lcsh:RC31-1245 ,Child ,Genetics (clinical) ,Hypohidrosis ,Genetic heterogeneity ,business.industry ,Altitude ,Native American ,Genomics ,medicine.disease ,Human genetics ,lcsh:Genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,Genomics analysis ,Mutation ,Female ,medicine.symptom ,business - Abstract
Background Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Case presentation Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. Conclusions This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.
- Published
- 2020
36. Análisis del potencial genotóxico y carcinógeno asociado a los cigarrillos electrónicos
- Author
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Andy Pérez-Villa, Ana Karina Zambrano, Jennyfer M. García-Cárdenas, Tiffany Cevallos-Vilatuña, Isaac Armendáriz Castillo, Paola E. Leone, César Paz y Miño, Patricia Guevara-Ramírez, Andrés López-Cortés, Antonella Vera-Guapi, Santiago Guerrero, and Verónica Yumiceba
- Subjects
Human health ,business.industry ,Environmental health ,Chemical abstracts service ,Oral epithelium ,Medicine ,General Medicine ,business - Abstract
Many studies, comparing the health associated risks of electronic cigarettes with conventional cigarettes, focus mainly on the common chemical compounds found between them. We therefore reviewed chemical compounds found exclusively in electronic cigarettes and describe their genotoxic and carcinogenic effects. The eligibility criteria included articles related exclusively to conventional and electronic cigarettes chemical composition. Articles which reported to be financed from cigarettes industries were excluded. Chemical compounds reported in the selected studies from conventional and electronic cigarettes were tabulated using the Chemical Abstracts Service registry number for chemical substances information. A total of 57 chemical compounds were exclusively reported to be present in electronic cigarettes. To further analyze e-cigarette carcinogenic effects, a gene set, previously reported to be deregulated in the oral epithelium of e-cigarettes users, was genomically analyzed in 32 PanCancer Atlas Studies. The crucial health risks identified were: eye, skin and respiratory tract irritation, with almost 50% of incidence. The main cancer risks associated with e-cigarettes were: ovarian, uterine, bladder, lung, esophageal and stomach carcinomas and adenocarcinomas. Despite being considered as less harmful for human health, the use of these devices is not recommended for first time users and it is considered hazardous for dual users.
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- 2020
37. Prediction of breast cancer proteins involved in immunotherapy, metastasis, and RNA-binding using molecular descriptors and artificial neural networks
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Alejandro Cabrera-Andrade, Andrés López-Cortés, César Paz-y-Miño, Cristian R. Munteanu, José M. Vázquez-Naya, Alejandro Pazos, Yunierkis Pérez-Castillo, Humberto Gonzáles-Díaz, Eduardo Tejera, and Santiago Guerrero
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lcsh:Medicine ,Breast Neoplasms ,Feature selection ,Computational biology ,Biology ,Article ,Metastasis ,Machine Learning ,Breast cancer ,Protein sequencing ,Molecular descriptor ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Metastasis ,lcsh:Science ,Multidisciplinary ,Artificial neural network ,Gene Expression Profiling ,lcsh:R ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Multilayer perceptron ,RNA ,lcsh:Q ,Female ,Immunotherapy ,Neural Networks, Computer - Abstract
[Abstract] Breast cancer (BC) is a heterogeneous disease where genomic alterations, protein expression deregulation, signaling pathway alterations, hormone disruption, ethnicity and environmental determinants are involved. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design. This work is proposing accurate prediction classifer for BC proteins using six sets of protein sequence descriptors and 13 machine-learning methods. After using a univariate feature selection for the mix of fve descriptor families, the best classifer was obtained using multilayer perceptron method (artifcial neural network) and 300 features. The performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980±0.0037, and accuracy of 0.936±0.0056 (3-fold cross-validation). Regarding the prediction of 4,504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1. This powerful model predicts several BC-related proteins that should be deeply studied to fnd new biomarkers and better therapeutic targets. Scripts can be downloaded at https://github.com/muntisa/ neural-networks-for-breast-cancer-proteins. This work was supported by a) Universidad UTE (Ecuador), b) the Collaborative Project in Genomic Data Integration (CICLOGEN) PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013-2016 and the European Regional Development Funds (FEDER) - “A way to build Europe”; c) the General Directorate of Culture, Education and University Management of Xunta de Galicia ED431D 2017/16 and “Drug Discovery Galician Network” Ref. ED431G/01 and the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23); d) the Spanish Ministry of Economy and Competitiveness for its support through the funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER) by the European Union; e) the Consolidation and Structuring of Competitive Research Units - Competitive Reference Groups (ED431C 2018/49), funded by the Ministry of Education, University and Vocational Training of the Xunta de Galicia endowed with EU FEDER funds; f) research grants from Ministry of Economy and Competitiveness, MINECO, Spain (FEDER CTQ2016-74881-P), Basque government (IT1045-16), and kind support of Ikerbasque, Basque Foundation for Science; and, g) Sociedad Latinoamericana de Farmacogenómica y Medicina Personalizada (SOLFAGEM) Xunta de Galicia; ED431D 2017/16 Xunta de Galicia; ED431G/01 Xunta de Galicia; ED431D 2017/23 Xunta de Galicia; ED431C 2018/49 Gobierno Vasco; IT1045-16
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- 2020
38. Tracing the genetic history of the 'Cañaris' from Ecuador and Peru using uniparental DNA markers
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Fabrício R. Santos, Spencer Wells, Ricardo Fujita, Marilza M. S. Jota, José R. Sandoval, César Paz-y-Miño, Daniela R. Lacerda, Pierina Danos, and Paulo Robles-Ruiz
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Genetic Markers ,Mitochondrial DNA ,Lineage (genetic) ,lcsh:QH426-470 ,Population genetics ,lcsh:Biotechnology ,SNP ,Genetic relationship ,Biology ,Y chromosome ,DNA, Mitochondrial ,03 medical and health sciences ,0302 clinical medicine ,lcsh:TP248.13-248.65 ,parasitic diseases ,Peru ,Genetics ,Humans ,030304 developmental biology ,0303 health sciences ,Chromosomes, Human, Y ,Indians, South American ,Research ,Haplotype ,Genetic Variation ,Cañaris ,lcsh:Genetics ,Genetics, Population ,Haplotypes ,Short tandem repeats ,Genetic marker ,Evolutionary biology ,Microsatellite ,Ecuador ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Background According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of Tawantinsuyu, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris–Inkawasi communities of a village, a former Inka camp, which persists until the present day. This scenario could explain these toponyms, but it is still controversial. To clarify this historical question, the study presented here focused on the inference of the genetic relationship between ‘Cañaris’ populations, particularly of Cañar and Ferreñafe, compared to other highland populations. We analysed native patrilineal Y chromosome haplotypes composed of 15 short tandem repeats, a set of SNPs, and maternal mitochondrial DNA haplotypes of control region sequences. Results After the genetic comparisons of local populations—three from Ecuador and seven from Peru—, Y chromosome analyses (n = 376) indicated that individuals from the Cañar region do not share Y haplotypes with the Kañaris, or even with those of the Inkawasi. However, some Y haplotypes of Ecuadorian ‘Cañaris’ were associated with haplotypes of the Peruvian populations of Cajamarca, Chivay (Arequipa), Cusco and Lake Titicaca, an observation that is congruent with colonial records. Within the Kañaris and Inkawasi communities there are at least five clans in which several individuals share haplotypes, indicating that they have recent common ancestors. Despite their relative isolation, most individuals of both communities are related to those of the Cajamarca and Chachapoyas in Peru, consistent with the spoken Quechua and their geographic proximity. With respect to mitochondrial DNA haplotypes (n = 379), with the exception of a shared haplotype of the D1 lineage between the Cañar and Kañaris, there are no genetic affinities. Conclusion Although there is no close genetic relationship between the Peruvian Kañaris (including Inkawasi) and Ecuadorian Cañar populations, our results showed some congruence with historical records.
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- 2020
39. Characterization Of Ancestral Origin Of Cystic Fibrosis Of Patients With New Reported Mutations In CFTR
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Andrés López-Cortés, Andy Pérez-Villa, Isaac Armendáriz-Castillo, Patricia Guevara-Ramírez, Juan Carlos Ruiz-Cabezas, Ana Karina Zambrano, César Paz-y-Miño, Paola E. Leone, Jennyfer M. García-Cárdenas, Verónica Yumiceba, and Santiago Guerrero
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0301 basic medicine ,Cystic Fibrosis ,Genotype ,Article Subject ,Population ,Cystic Fibrosis Transmembrane Conductance Regulator ,Ancestry-informative marker ,Biology ,medicine.disease_cause ,Cystic fibrosis ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,education ,Genetics ,Principal Component Analysis ,education.field_of_study ,Mutation ,General Immunology and Microbiology ,Native american ,Incidence (epidemiology) ,Racial Groups ,General Medicine ,medicine.disease ,Obstructive lung disease ,030104 developmental biology ,030228 respiratory system ,Medicine ,Ecuador ,Research Article - Abstract
The incidence of cystic fibrosis (CF) and the frequency of the variants reported for CFTR depend on the population; furthermore, CF symptomatology is characterized by obstructive lung disease and pancreatic insufficiency among other symptoms, which are reliant on the individual's genotype. The Ecuadorian population is a mixture of Native Americans, Europeans, and Africans. That population admixture could be the reason for the new mutations reported in a previous study by Ruiz et al. (2019). A panel of 46 Ancestry Informative Markers was used to estimate the ancestral proportions of each available sample (12 samples in total). As a result, the Native American ancestry proportion was the most prevalent in almost all individuals, except for three patients from Guayaquil with the mutation [c.757G>A:p.Gly253Arg; c.1352G>T:p.Gly451Val] who had the highest European composition.
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- 2020
40. Gen DRD2, TH y DTNBP1 y la sintomatología de pacientes ecuatorianos esquizofrénicos tratados con haloperidol. Caso Clínico
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Fabián Porras-Borja, César Paz-y-Miño, Camilo Pérez, Erickson Toscano, and Paola E. Leone
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Genetic variants of chemical neurotransmission have been associated with the development of schizophrenia. This is a syndromic mental disorder that affects the perception of reality and feelings of those affected. This disease is expressed in 1% of the world’s population; in all cases, antipsychotic drugs are used as treatment. Scientific evidence indicates that symptomatologic characteristics and therapeutic response has a genetic influence. The objective of the current work was to describe the presence or absence of allelic polymorphisms found on the dopamine gene and the therapeutic response of 11 Ecuadorian individuals treated with haloperidol (5mg.), for a period of 14 days. Single Nucleotide Polymorphisms (SNPs) in the DRD2, TH and DTNBP1 genes and evaluations recorded from the PANSS, BPRS and UKU scales were assessed. An association with a significance of P = 0.024 was found between the Taq1-B polymorphism on the DRD2 gene and the BPRS positive symptom scale; furthermore, an association with a significance of P = 0.045 was found with the PANSS negative symptoms scale. The absence of the Ser311Cys polymorphism on the DRD2 gene within the sample was also reported. In conclusion, it is noted that there is a statistically significant difference between the symptomatologic group, individuals with allele A / G SNP Taq1-B, and the group of individuals without the polymorphism. Even though the biological mechanisms behind this result are not understood, his study will serve as a basis for the development of future research related to this topic.
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- 2020
41. TCGA Pan-Cancer genomic analysis of Alternative Lengthening of Telomeres (ALT) related genes
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Andy Pérez-Villa, Patricia Guevara-Ramírez, Jennyfer M. García-Cárdenas, Paola E. Leone, Verónica Yumiceba, Isaac Armendáriz-Castillo, Santiago Guerrero, César Paz-y-Miño, Andrés López-Cortés, and Ana Karina Zambrano
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0301 basic medicine ,Telomerase ,lcsh:QH426-470 ,ALT ,In silico ,Telomere-Binding Proteins ,Genomics ,Computational biology ,Biology ,Article ,Homology directed repair ,03 medical and health sciences ,0302 clinical medicine ,Telomere Maintenance Gene ,Neoplasms ,Genetics ,Humans ,cancer ,Genetic Predisposition to Disease ,Protein Interaction Maps ,Gene ,Genetics (clinical) ,Telomere Homeostasis ,telomeres ,Telomere ,lcsh:Genetics ,030104 developmental biology ,in silico ,030220 oncology & carcinogenesis ,Cancer cell ,Homologous recombination - Abstract
Telomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85&ndash, 90% reactivate telomerase, while 10&ndash, 15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors switch from a telomerase-dependent mechanism to ALT, in fact, the co-existence between both mechanisms has been observed in some cancers. Although different elements in the ALT pathway are uncovered, some molecular mechanisms are still poorly understood. Therefore, with the aim to identify potential molecular markers for the study of ALT, we combined in silico approaches in a 411 telomere maintenance gene set. As a consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies from The Cancer Genome Atlas and found 325,936 genomic alterations, from which, we identified 20 genes highly mutated in the cancer studies. Finally, we made a protein-protein interaction network and enrichment analysis to observe the main pathways of these genes and discuss their role in ALT-related processes, like homologous recombination and homology directed repair. Overall, due to the lack of understanding of the molecular mechanisms of ALT cancers, we proposed a group of genes, which after ex vivo validations, could represent new potential therapeutic markers in the study of ALT.
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- 2020
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42. OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine
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Alejandro Pazos, Stephen J. Barigye, Andrés López-Cortés, Humberto González-Díaz, César Paz-y-Miño, Cristian R. Munteanu, Alejandro Cabrera-Andrade, Yunierkis Pérez-Castillo, Eduardo Tejera, and Santiago Guerrero
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Proteome ,lcsh:Medicine ,Breast Neoplasms ,Computational biology ,Disease ,Biology ,Interactome ,Article ,MED1 ,Mice ,Breast cancer ,Trastuzumab ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Cancer genomics ,medicine ,Animals ,Humans ,Gene Regulatory Networks ,Protein Interaction Maps ,Precision Medicine ,PLCG1 ,lcsh:Science ,Gene ,Genes, Essential ,Multidisciplinary ,Molecular medicine ,lcsh:R ,High-Throughput Nucleotide Sequencing ,Cancer ,Prognosis ,medicine.disease ,Precision medicine ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Docetaxel ,Pharmacogenomics ,Mutation ,Cancer research ,Female ,lcsh:Q ,Tamoxifen ,medicine.drug - Abstract
Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.
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- 2020
43. Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis
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Alejandro Pazos, Humbert González-Díaz, Yunierkis Pérez-Castillo, Gabriela Jaramillo-Koupermann, Andrés López-Cortés, César Paz-y-Miño, Cristian R. Munteanu, Eduardo Tejera, and Alejandro Cabrera-Andrade
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life_sciences_other ,Consensus ,gene prioritization ,DNA Repair ,DNA repair ,DNA damage ,Bone Neoplasms ,Computational biology ,Pathogenesis ,Biology ,Article ,Catalysis ,communality analysis ,lcsh:Chemistry ,Inorganic Chemistry ,Interaction network ,Early recognition ,osteosarcoma ,medicine ,Humans ,Gene Regulatory Networks ,Protein Interaction Maps ,CHEK1 ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Gene ,Spectroscopy ,PI3K/AKT/mTOR pathway ,Osteosarcoma ,pathogenesis ,Organic Chemistry ,Computational Biology ,General Medicine ,Cell cycle ,medicine.disease ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,early recognition ,Gene Ontology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene prioritization ,Communality analysis ,Signal Transduction - Abstract
Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma, however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein&ndash, protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.
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- 2020
44. Metastatic signaling of hypoxia-related genes across TCGA Pan-Cancer types
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Andy Pérez-Villa, Jennyfer M. García-Cárdenas, César Paz-y-Miño, Yumiceba, Santiago Guerrero, Andrés López-Cortés, Isaac Armendáriz-Castillo, Córdova-Bastidas D, Esteban Ortiz-Prado, Ana Karina Zambrano, Patricia Guevara-Ramírez, Paola E. Leone, and Nelson Varela
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Tumor hypoxia ,ErbB ,medicine ,Cancer research ,Disease ,Signal transduction ,Biology ,Hypoxia (medical) ,medicine.symptom ,medicine.disease ,Interactome ,PI3K/AKT/mTOR pathway ,Metastasis - Abstract
Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis. Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Here we focused on elucidating the molecular hallmarks of tumor hypoxia that remains poorly defined. To fill this gap, we analyzed the genomic alterations and hypoxia score of 233 hypoxia-related genes of 6,343 individuals across 17 TCGA Pan-Cancer types. In addition, we analyzed a protein-protein interactome (PPi) network and the shortest paths from hypoxic proteins to metastasis. As results, mRNA high alteration was prevalent in all cancer types. Genomic alterations and hypoxia score presented a highest frequency in tumor stage 4 and positive metastasis status in all cancer types. The most significant signaling pathways were HIF-1, ErbB, PI3K-Akt, FoxO, mTOR, Ras and VEGF. The PPi network revealed a strong association among hypoxic proteins, cancer driver proteins and metastasis driver proteins. The analysis of shortest paths revealed 99 ways to spread metastasis signaling from hypoxic proteins. Additionally, we proposed 62 hypoxic genes strongly associated with metastasis and 27 of them with high amount of genomic alterations. Overall, tumor hypoxia may drive aggressive molecular features across cancer types. Hence, we identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at improving novel drug development and treating metastasis.
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- 2020
45. Microfiltraciones entre ionómero de vidrio y resina compuesta en lesiones clase-V no cariosas
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Eliana Carolina Morillo-Cárdenas, Jennyfer M. García Cárdenas, María Elena Flores-Araque, César Paz-y-Miño, and Paola E. Leon
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cemento de Ionómero Vítreo ,lcsh:RK1-715 ,lcsh:Dentistry ,lcsh:R ,Recubrimiento de la Cavidad Dental ,lcsh:Medicine ,Filtración dental ,adaptación marginal dental ,resinas compuestas - Abstract
No se han establecido estándares para el tratamiento de cavidades cervicales no cariosas; un biomaterial adecuado permitirá buena adaptación y longevidad de la restauración. Objetivo: Determinar la microfiltración en cavidades clase V no cariosas restauradas con ionómero de vidrio y resina nanoparticulada. Materiales y métodos: Cavidades clase V realizadas en la superficie vestibular de 80 premolares sanos (1,5 mm de profundidad x 3 mm de altura en sentido ocluso- gingival x 2 mm de ancho en sentido mesio-distal) se restauraron aleatoriamente con dos biomateriales (n = 40): 1) ionómero de vidrio y 2) resina de nano relleno. Después, los especímenes fueron aislados con barniz y sumergidos en azul de metileno por 24 horas. Posteriormente, las muestras se sometieron 500 ciclos de termociclado por 8 horas y 45 minutos con cambios térmicos de 37°, 72° y 75°C, cada ciclo con una duración de 17 segundos. Las muestras fueron lavadas con agua destilada y seccionadas longitudinalmente para determinar el grado de microfiltración utilizando un estereoscopio (Leica M60, Biosystems). Los datos categóricos se analizaron con el test Chi2 en SPSS 24®. Resultados: Se pudo apreciar que la filtración es significativamente menor en resina que con ionómeros de vidrio (p < 0,001). Sin embargo, ninguno de los materiales de restauración probados fue capaz de sellar los márgenes o las paredes de los dientes completamente. Conclusión: como resultado del presente experimento se determina que las restauraciones de clase V obturadas con resina de nano relleno presentan menor microfiltración marginal que las restauradas con ionómero de vidrio.
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- 2020
46. Cytogenetic and genomic analysis of a patient with turner syndrome and t(2;12): a case report
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Andy Pérez-Villa, Verónica Yumiceba, Ana Karina Zambrano, Jennyfer M. García-Cárdenas, Patricia Guevara-Ramírez, Andrés López-Cortés, Paola E. Leone, Santiago Guerrero, Jesús M. Hernández-Rivas, Ariana Jijón-Vergara, Isaac Armendáriz-Castillo, Juan Luis García, and César Paz-y-Miño
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0301 basic medicine ,medicine.medical_specialty ,Monosomy ,lcsh:QH426-470 ,Genetic counseling ,Turner syndrome ,síndrome de Turner ,Case Report ,030209 endocrinology & metabolism ,Chromosomal translocation ,Biology ,Biochemistry ,03 medical and health sciences ,Cytogenetics ,0302 clinical medicine ,FISH ,Genetics ,medicine ,Molecular Biology ,Genetics (clinical) ,X chromosome ,Autosome ,2409 Genética ,citogenética ,Biochemistry (medical) ,Genetic disorder ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,Genetic mapping arrays ,Reciprocal translocation ,Molecular Medicine ,2414 Microbiología - Abstract
Background Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool. Conclusion To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.
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- 2020
47. La problemática de la investigación nacional y los aspectos éticos involucrados
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Ivonne Ochoa García and César Paz y Miño
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ética ,investigación ,lcsh:Public aspects of medicine ,científica ,lcsh:RA1-1270 ,normativa ,burocracia - Abstract
En objetivo de este artículo, es construir una visión actual de la realidad investigativa frente a los principales actores de la investigación científica con seres humanos en el Ecuador y su ética en el desarrollo de ciencia. Analiza la situación actual de la normativa legal y reglamentaria que intervienen en el desarrollo científico y la necesidad de conseguir que la investigación constituya una actividad de impulso y formación en las universidades e instituciones. Se plantea que la investigación nacional está aquejada de trabas, nuevas y más sofisticadas, regulaciones, controles internos inadecuados y punitivos, desconocimiento del derecho intrínseco y autónomo de instituciones e investigadores, lo que lleva a que la producción en ciencia sea muy escaza.
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- 2019
48. Prediction of breast cancer proteins using molecular descriptors and artificial neural networks: a focus on cancer immunotherapy proteins, metastasis driver proteins, and RNA-binding proteins
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Yunierkis Pérez-Castillo, José M. Vázquez-Naya, Alejandro Pazos, Alejandro Cabrera-Andrade, Andrés López-Cortés, Cristian R. Munteanu, Humberto Gonzáles-Díaz, César Paz-y-Miño, Eduardo Tejera, and Santiago Guerrero
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Protein sequencing ,Breast cancer ,Artificial neural network ,Cancer immunotherapy ,Molecular descriptor ,medicine.medical_treatment ,medicine ,Feature selection ,RNA-binding protein ,Computational biology ,Biology ,medicine.disease ,Metastasis - Abstract
BackgroundBreast cancer (BC) is a heterogeneous disease characterized by an intricate interplay between different biological aspects such as ethnicity, genomic alterations, gene expression deregulation, hormone disruption, signaling pathway alterations and environmental determinants. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design.MethodsThis work is proposing accurate prediction classifier for BC proteins using six sets of protein sequence descriptors and 13 machine learning methods. After using a univariate feature selection for the mix of five descriptor families, the best classifier was obtained using multilayer perceptron method (artificial neural network) and 300 features.ResultsThe performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980 ± 0.0037 and accuracy of 0.936 ± 0.0056 (3-fold cross-validation). Regarding the prediction of 4504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1.ConclusionsThis powerful model predicts several BC-related proteins which should be deeply studied to find new biomarkers and better therapeutic targets. The script and the results are available as a free repository athttps://github.com/muntisa/neural-networks-for-breast-cancer-proteins.
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- 2019
49. Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review
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Jesús María Hernández-Rivas, Juan Luis García, César Paz-y-Miño, Paola E. Leone, Stella D Verdezoto, and Ana Proaño
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0301 basic medicine ,lcsh:Internal medicine ,Microcephaly ,lcsh:QH426-470 ,Ring chromosome ,Chromosome Disorders ,Case Report ,030105 genetics & heredity ,Biology ,Ring (chemistry) ,Short stature ,03 medical and health sciences ,FISH ,Genetics ,medicine ,Humans ,Ring Chromosomes ,lcsh:RC31-1245 ,Child ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Low-set ears ,inv dup del rearrangement ,medicine.diagnostic_test ,Karyotype ,medicine.disease ,Human genetics ,lcsh:Genetics ,030104 developmental biology ,Karyotyping ,Cytogenetic Analysis ,Female ,Chromosomes, Human, Pair 4 ,medicine.symptom ,46,XX,r(4)(p16.3q35.2) ,Mosaic ,Mapping array ,Ring chromosome 4 ,Fluorescence in situ hybridization - Abstract
Background Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical “ring syndrome.”
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- 2019
50. Chemoinformatics Profiling of the Chromone Nucleus as a MAO-B/A2AAR Dual Binding Scaffold
- Author
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Fernanda Borges, M. Natália D. S. Cordeiro, Yunier Perera-Sardiña, Maykel Cruz-Monteagudo, Aminael Sánchez-Rodríguez, Aliuska Morales Helguera, Eduardo Tejera, César Paz-y-Miño, and Yunierkis Pérez-Castillo
- Subjects
0301 basic medicine ,Scaffold ,Monoamine Oxidase Inhibitors ,Receptor, Adenosine A2A ,A2A adenosine receptor ,Adenosine A2A receptor ,Computational biology ,chemoinformatics ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,dual-target binder ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Monoamine Oxidase ,Pharmacology ,Virtual screening ,Drug discovery ,Chemistry ,chromones ,Parkinson Disease ,General Medicine ,Adenosine A2 Receptor Antagonists ,Molecular Docking Simulation ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,parkinson´s disease ,Neurology ,Cheminformatics ,Chromone ,monoamine oxidase B ,Neurology (clinical) ,Monoamine oxidase B ,Nucleus ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Background In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson's disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A2A receptor (A2AAR) blockade, as a promising approach to prevent the neurodegeneration involved in PD. Currently, only two chemical scaffolds has been proposed as potential dual MAO-B inhibitors/A2AAR antagonists (caffeine derivatives and benzothiazinones). Methods In this study, we conduct a series of chemoinformatics analysis in order to evaluate and advance the potential of the chromone nucleus as a MAO-B/A2AAR dual binding scaffold. Results The information provided by SAR data mining analysis based on network similarity graphs and molecular docking studies support the suitability of the chromone nucleus as a potential MAOB/ A2AAR dual binding scaffold. Additionally, a virtual screening tool based on a group fusion similarity search approach was developed for the prioritization of potential MAO-B/A2AAR dual binder candidates. Among several data fusion schemes evaluated, the MEAN-SIM and MIN-RANK GFSS approaches demonstrated to be efficient virtual screening tools. Then, a combinatorial library potentially enriched with MAO-B/A2AAR dual binding chromone derivatives was assembled and sorted by using the MIN-RANK and then the MEAN-SIM GFSS VS approaches. Conclusion The information and tools provided in this work represent valuable decision making elements in the search of novel chromone derivatives with a favorable dual binding profile as MAOB inhibitors and A2AAR antagonists with the potential to act as a disease-modifying therapeutic for Parkinson's disease.
- Published
- 2017
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