Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
Browse
Search Results
- Phylotranscriptomic Analysis of Pigment Biosynthesis in the Caryophyllales(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024-12-02) Gutierrez Vences, Alma Yesenia; Rodríguez López, Carlos Eduardo; Chavez Santoscoy, Rocío; Dang, Thu-Thuy; Díaz de la Garza, Rocío; Treviñp, Manuel; School of Engineering and Sciences; Campus MonterreyIn plants, color is given by secondary metabolites, pigments, that absorb and emit color due to their chemical structure. Betalains are a class of tyrosine-derived pigments found exclusively in the Caryophyllales order, where they are concurrent with the anthocyanin pigments. These two types of pigments show a mutually exclusive pattern of expression rooted in a complex homoplastic distribution. Although the genetic events that led to the emergence of betalains in the Caryophyllales is known, the exact genetic evolutionary path that led to mutual exclusion remains elusive with multiple theories with a single or multiple emergences being proposed. This thesis combines orthology-based phylogenetic correlation analyses with comparative transcriptomics to investigate the molecular and evolutionary drivers of pigment biosynthesis, focusing on transcriptional regulation, pigment structural modification, and transport mechanisms. Co-expression analysis revealed potential regulatory co-option, suggesting that betalain-producing species may have repurposed ancestral anthocyanin regulatory mechanisms to drive their pigment emergence. Additionally, candidate enzymes such as UGT, SCPL, and MT were identified as key players in pigment structural modification and stabilization in betalain-producing species. The research also presents novel insights into the role of cellular transport mechanisms in pigment exclusion. Genes in orthogroups with statistically different occupancy annotated in processes related to vesicle trafficking were found to coexpress with biosynthetic modules, suggesting that transport may contribute significantly to the mutual exclusion of anthocyanins and betalains. These findings hint at a possible loss and co-option of anthocyanin transport mechanisms for betalain sequestration in vacuoles, raising questions about how shifts in transport specificity may drive pigment divergence.
- Estimation of ancestry in the mexican population using informative genetic markers(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024) Valdez Alvarez, Héctor; Treviño Alvarado, Víctor Manuel; emipsanchez; Orozco Orozco, Lorena Sofía; García Ortiz, Humberto; Martínez Ledesma, Juan Emmanuel; Escuela de Ingeniería y Ciencias; Campus Monterrey; Garza Hernández, DeboraThe study of genetic ancestry has become an essential component of modern genetics, offering insights into the origins and migrations of human populations. This thesis presents the development of a genetic ancestry panel specifically tailored for the Mexican population, a group characterized by its high genetic diversity and complex admixture. The primary objective of this research is to accurately estimate the proportions of ancestry in Mexicans using informative genetic markers, thereby addressing the underrepresentation of this population in Genome-Wide Association Studies (GWAS). In the initial phase, various genetic databases were considered, and three were selected for the development of the ancestry panel: the 1000 Genomes Project (1000G), the Human Genome Diversity Project (HGDP), and the Metabolic Analysis in an Indigenous Sample (MAIS). The integration of these datasets provided a comprehensive view of genetic diversity crucial for the panel's accuracy. Principal Component Analysis (PCA) was employed to visualize the genetic structure and verify the separation of ancestral groups. The results confirmed the integrity of the selected datasets. Three methods for selecting Ancestry Informative Markers (AIMs)—Top K, Balanced K, and SumInfo K—were developed and evaluated. Although Balanced K and SumInfo K showed better performance than Top K, integrating Mexican data (MAIS) posed significant challenges, particularly due to the influence of East Asian populations. To address these issues, a revised strategy was implemented, focusing on optimizing AIM selection and improving the robustness of the panel. This involved a detailed workflow and validation process, ensuring the final panel's reliability. Despite the challenges, the new strategy demonstrated promising results, and the final panel is expected to be completed soon. The developed ancestry panel has significant implications for forensic science, personalized medicine, and anthropological research. By accurately estimating ancestry proportions in the Mexican population, this research contributes to a broader understanding of genetic diversity and supports more effective medical and forensic applications. Future work will focus on finalizing the panel and applying it to the oriGen project, which aims to analyze genetic data from a large cohort of Mexicans, further enhancing the understanding of this population's genetic landscape.
- Analysis of cellular senescence in Spinocerebellar ataxia type 7 using bioinformatics and an inducible cell model(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2022-06-15) Ruiz Esparza Palacios, Vanessa; GONZALEZ MELJEM, JOSE MARIO; 316764; González Meljem, José Mario; puemcuervo; Pérez Méndez, Óscar Armando; García Aguirre, Ian Alaín; School of Engineering and Sciences; Campus Monterrey; Magaña Aguirre, Jonathan JavierSpinocerebellar ataxia type 7 (SCA7) is an autosomal dominant inherited disorder manifested by the inability to coordinate balance, gait, and speech. Some experimental evidence suggests that nuclear inclusion of mutant ataxin-7 (ATX7) is part of the molecular basis of this disease and the origin of oxidative stress. In this thesis, we made a bioinformatic analysis that supports the hypothesis that SCA7 could share some mechanisms that are core features of senescent cells. Senescence is a permanent state of cell-cycle arrest, and core features of this phenotype include the expression of anti-proliferative molecules, the activation of a chronic DNA damage response, altered metabolic rates, and many others. We sought to establish a senescence induction protocol in a human fibroblast cell line as a positive control of senescence and found that induction with H2O2 at 1200 μM resulted in 79% of positive SA-β-gal cells. Afterwards, we were able to validate an inducible cell model of MIO-M1 cells, which were stably transduced to express a mutant ATXN7 gene carrying 64 CAG repeats and 10 CAG repeats. Administration of doxycycline (dox) induced the expression of the mutated protein causing the formation of nuclear aggregates. Furthermore, in a preliminary SA-β-gal assay, we found activity of this enzyme in 64 CAG cells, suggesting the presence of senescence features after the induction of the mutated protein. Based on our findings, we propose that the oxidative stress generated by the accumulation of the mutated protein could be leading to a senescence phenotype. Future evaluation of the Senescence-associated secretory phenotype (SASP) and markers of DNA damage will bring better understanding of the possible role of senescence in SCA7.
- Bioinformatic analysis of the expression pattern of an intron-retaining isoform of the Agrp transcript in arcuate nucleus neurons of mice(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-12-07) Gómez Montalvo, Jesús; GONZALEZ MELJEM, JOSE MARIO; 316764; González Meljem, José Mario; puemcuervo, emipsanchez; Treviño Alvarado, Víctor Manuel; de Obeso Fernández del Valle, Álvaro; School of Engineering and Sciences; Campus Monterrey; Avendaño Vázquez, Selma EréndiraKnown to be the regulatory center of hunger and satiety, the arcuate nucleus (ARC) harbors two neuronal populations that exert opposite effects on the regulation of food intake. Namely, AgRP and POMC neurons respectively trigger hunger and satiety. Although both neuronal groups are born within the same time interval in the developing hypothalamus of mouse, their peptidergic identities are established at distinct developmental timepoints. While the POMC identity is established as early as the embryonic period, the complete maturation of the AgRP peptidergic identity extends to the postnatal period. Previously, through RT-PCR, our group detected the presence of an Agrp transcript isoform that retained introns 3 and 4 (Agrp-i3,4) in the early postnatal, but not in the adult mouse hypothalamus. In this thesis project, the expression pattern of Agrp-i3,4 is analyzed in public RNA-seq datasets from ARC neurons of mice at different postnatal developmental stages. To identify intron retention events, iREAD was used, and to quantify the proportion of Agrp transcripts that retained introns 3 and 4, ASpli was employed. Using this bioinformatics approach, the largest proportion of Agrp-i3,4 was detected in ARC samples of P12 mice and there was a trend towards decreased retention of Agrp introns 3 and 4 at later developmental stages. Agrp-i3,4 was detected in poly-A RNA extracted from whole AgRP neurons, but not in the ribosomal fraction. On the other hand, food deprivation appeared to exert distinct effects on the proportion of the Agrp-i3,4 transcript depending on the duration of the fast. While in weaned mice fasted for 16 hours Agrp-i3,4 showed a slight increase, in adult mice fasted for 38 hours Agrp-i3,4 appeared to decrease. Unlike fasting, leptin treatment did not exert any effect on the retention of Agrp introns 3 and 4. Of note, IR was found in Agrp but not in other genes that characterize the ARC, such as Npy or Pomc. Taken together, the results presented in this thesis suggest that increased IR of the Agrp transcript may correlate with a lower maturation degree of the ARC during a time interval in which the AgRP peptidergic identity has not yet been fully established.
- Antimicrobial resistance prediction by bacterial genome-wide-association-study in non-fermenting bacilli with critical priority (Pseudomonas aeruginosa and acinetobacter baumannii).(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-12-07) Barlandas Quintana, Erick Alan; MARTINEZ LEDESMA, JUAN EMMANUEL; 200096; Martinez Ledesma, Juan Emmanuel; puemcuervo; González Mendoza, Miguel; Garza González, Elvira; School of Engineering and Sciences; Campus Estado de México; Cuevas Díaz Durán, RaquelAntimicrobial resistance (AMR) (or drug resistance) is a natural phenomenon where microor- ganisms change their molecular, physical, or chemical structures to resist the drugs created by infections. The World Health Organization (WHO) had released for the first time a list of Multidrug-Resistant Bacteria (MRB) that pose the greatest threat to human health and for which new antibiotics are desperately needed. Acinetobacter baumannii and Pseudomonas aeruginosa resistant to carbapenems are part of the Gram-negative non-fermenting bacilli group with critical priority according to the WHO. For this, the final research purpose was to create and train a bioinformatic study capable of finding critical k-mers that could differentiate those strains of P. aeruginosa and A. baumannii resistant to carbapenems. Four k-mers sizes were performed for each bacterium (12, 14, 16, and 18), and two training and testing (70:30 and 80:20) schemas were used over seven different machine learning algorithms: Random Forrest, Adaboost, Xgboost, Decision Trees, Bagging Classifier, Support Vector Machine, and KNN. For both bacteria, the best models were obtained when using a k-mer length of 12. In the case of Acinetobacter baumannii, the best models obtained an accuracy of 0.99 for testing. Moreover, for Pseudomonas aeruginosa, the best accuracy obtained was 0.93 when us- ing Bagging Classifier. To investigate the sequences of the k-mers obtained, the National Cen- ter for Biotechnology Information (NCBI) Basic Local Alignment Search Tool BLAST was used. Ten to twenty sequences built with the k-mers were investigated for each model. When using a k-mer length of 12 for A. baumannii, 18 out of 20 sequences represented a crucial sequence in carbapenems (meropenem and imipenem) resistance. In the case of P. aerugi- nosa, 16 out of 20 sequences represented a key sequence. To complement this research, a Dynamic Programming algorithm was used to find changes over the reference genome that could explain the carbapenems resistance within the resistant genomes. Not all the resistant k-mer sequences were found over the reference genome, as some of them could be acquired by horizontal transference (Conjugation, Transformation, or Transduction inheritance). Fur- ther investigation over these sequences can be applied in creating new directed antibiotics or detecting easily resistant strains of Pseudomonas aeruginosa or Acinetobacter baumannii resistant to carbapenems.
- In silico identification of cis-regulatory elements in folate biosynthesis and 1C metabolism genes in plants(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-11-26) Salinas Espinosa, Jessica Pamela; TREVIÑO ALVARADO, VICTOR MANUEL; 205076; Treviño Alvarado, Víctor Manuel; puemcuervo; Cuevas Díaz Durán, Raquel; Rodríguez López, Carlos; Martínez Ledesma, Juan Emmanuel; School of Engineering and Sciences; Campus Monterrey; Díaz de la Garza, Rocío IsabelFolates (vitamin B9) are enzyme cofactors required for all organisms for one-carbon (1C) transfer reactions. A deficiency of these nutrients can lead to several health problems. Since humans are not natural producers of folates, the intake of these nutrients from plants is vital for human nutrition. Several techniques that involve the genetic modification of organisms have proved to be effective for the fortify plants with essential macronutrients. However, to achieve this, it is necessary to elucidate the metabolic control in plant systems. Although the genes involved in folate biosynthesis and 1C metabolism in plants are known, the mechanisms of transcriptional regulation have not yet been explored. This project focuses on discovering cis-regulatory DNA elements (motifs) using computational data analysis to provide insights regarding the regulation of folate biosynthesis in plants. For this, we first collected a compendium of known genes related to folate biosynthesis. Then, a database comprising the DNA promoter regions of folate biosynthesis and 1C metabolism genes in 19 different plant species was built and analyzed using different motif discovery algorithms. Afterward, the discovered motifs were tested for statistical significance and further associated with their putative biological role using other bioinformatics tools. A total of 149 statistically significant motifs (p < .05) were discovered in 18 of 19 species using the GimmeMotifs ensemble algorithm. These motifs were represented in 104 different regulatory networks built automatically from co-expression clusters obtained from each plant species. The results from this work could provide an insight into the transcriptional regulation of the folate biosynthesis pathway in plants. Furthermore, the elements found could be used for research in gene editing techniques to produce biofortified crops.
- The role of HDL and phospholipids in endothelial cellular senescence(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-05-26) De la Cruz Gutiérrez, Luis Fernando; DE LA CRUZ GUTIERREZ, LUIS FERNANDO; 672038; González Meljem, José Mario; puemcuervo; Magaña Aguirre, Jonathan Javier; Chávez Santos, Rocío Alejandra; School of Engineering and Sciences; Campus Monterrey; Pérez Méndez, Oscar ArmandoHigh-density lipoproteins (HDLs) are commonly recognized as antiatherogenic molecules; these possess anti-inflammatory properties and participate in the production of Nitric Oxide (NO) by endothelial cells. In addition, critical patients characterized by a dropdown of HDL-cholesterol plasma levels during the acute phase, have an increased risk of intrahospital death. The molecular mechanisms underlying the beneficial effects of HDL are not well understood. However, current clinical evidence suggests a relationship between HDL and cellular senescence, a stress response characterized by a mostly irreversible loss in the replicative potential of the cell. This permanent cell cycle arrest can be induced through a variety of stimuli including telomere shortening, oxidative stress, DNA damage and oncogenic signals. At the organismal level, senescence contributes to aging and has been associated with numerous age-related pathologies. Now, few studies have documented that cellular senescence exhibits an alteration in lipid composition, leading to morphological changes in membrane remodeling. Additionally, a relationship between the altered expression of regulatory genes of lipid metabolism and senescent cells has been recently uncovered. Therefore, here we aimed to analyze the role of HDLs in endothelial cell senescence induced by doxorubicin and hydrogen peroxide. The results reveal that there is a possible impact of HDL on the onset of cellular senescence, although this may be more associated with membrane homeostasis, as reflected in a decrease in the number of cells positive for the senescence marker SA-β-galactosidase, as well as a decrease in apoptosis associated with the stress generated by the senescence inducer. However, further study of these lipoproteins in senescent cells is needed. Likewise, this study opens the door to consider hydrogen peroxide as a strong candidate to induce senescence in HMEC-1 endothelial cells derived from the oxidative stress that these cells can encounter physiologically.
- Association of gene expression signatures with genomic alterations and clinical outcomes(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-11-01) Ramos García, Axel Alejandro; MARTINEZ LEDESMA, JUAN EMMANUEL; 200096; Martínez Ledesma, Juan Emmanuel; puelquio, emipsanchez; Treviño Alvarado, Víctor Manuel; Cuevas Díaz Durán, Raquel; Aguirre Gamboa, Raúl; Escuela de Ingeniería y Ciencias; Campus MonterreyTechnological advances applied to molecular biology, have led this discipline to perform several and more complex experiments, which outcomes have been summarized within massive databases, provoking the emergence of new disciplines as well as innovative approaches to analyze this bunch of data. One of these disciplines is Bioinformatics, where high-throughput data have been utilized to understand some diseases, such as cancer, which has been studied in order to provide a better classification, diagnosis, and provide new possible treatments to this condition. Available data go, from whole-genome sequencing to tissue images, proteomic, and metabolomic, etc. In the case of gene expression profiles, one of the most utilized study approaches is the performance of single-gene analysis, a test which consists in the measurement of the level of expression gene by gene, carrying out a comparison between the case and control samples by a statistical method (t-test, Wilcoxon-rank-sum), to assign a p-value related to every gene, then by a threshold filter process, we will be able to identify significant genes, and finally, proceed to give a biological interpretation from obtained results. However, this approach presents some lacks, within which, we can mention: Due to the adjustment process, (necessary for the number of tests performed) can lead to information loss, labeling wrongly as false-negative some relevant genes. The use of arbitrary threshold values, provokes discoveries to be falsely positive if the values for higher values or false negatives for lower values. Modifications in biological processes are related to groups of genes, thus, measuring the variation of the expression level of these groups of genes will let us to give a better biological interpretation. These groups of genes have been identified and nowadays we can find them within several public databases, these collections of gene sets are known as gene-set, and they could be used to provide better insight when analyzing expression data. Thus, the purpose of this thesis was to find, if the score-gotten through single-sample gene set enrichment analysis from the bibliography, Hallmark, Oncogenic, CMAP Up, CMAP Down collections is relevant to perform cancer subtype-classification by unsupervised learning techniques (Hierarchical clustering), identify involved pathways in the gene mutation presence or absence. Finally, re- late this score with the survival probability, we were able to determine the life expectancy of people and candidate treatment drugs, based on the level of expression from the determined gene set, related to a specific biological process, chemical alteration, or aberration.
