Proyectos

PROPOSAL ABSTRACT: Traditional archaeology proposes that the first settlers of South America moved preferentially along the Andes or the Pacific coast. Given that the Andean Puna (>3,000 masl) was an outstanding ecological megapatch that concentrated similar resources throughout the Andes, it was an attractive migratory route. This paved the way for the establishment of a unique Altiplano socio-ecological system, which later became the cradle of more complex cultural developments. Stable resources, temperate climate and relatively easy movements along the coastline has made the Pacific coast an even stronger candidate to explain early human dispersal and the construction of long-term cultural niche. In contrast, the Intermediate Depression in the hyperarid core of the Atacama Desert, between the Pacific coast and the Andes has not been perceived as a sufficiently productive enough ecosystem to support early human settling and dispersion. Theoretically, it has been assumed that it was used as an area of complementary resources for both coastal and Andean hunter-gatherer societies. In this proposal, we expect to show that this traditional view is incorrect and propose that the Intermediate Depression was not just an area of complementary resources and a barrier for human dispersal. On the contrary, we aim to provide new data showing how this region facilitated local settling and the expansion of H. sapiens into different ecosystems of South America, as it acted as an interglacial ecological refuge. Moreover, we propose that, despite an almost complete lack of rainfall, the Pampa del Tamarugal (PdT) was a much more productive and complex ecosystem during the Pleistocene-Holocene transition than today. Well-dated early residential areas, along with certain geomorphological and hydroclimatic features such as high watertable, mild temperatures and relatively warm winters generated extensive and diverse wetlands, creating some enclaves of the PdT very attractive compared to other regions. One of our main goals is to find these places, and ecologically and culturally characterize them. Conversely, we will investigate the potential of this basin as a glacial refuge a self-contained ecosystem that harbored many species of plants and animals that today occur at higher elevations, and uniquely suited to sustain small populations of hunter-gatherers that moved into the region, who then adopted and transformed this environment into their home. In this context, this proposal aims to research and understand how human societies developed long-term residential systems in a former ecological refuge withing this hyperarid desert. By describing and analyzing the dynamically productive environmental conditions of the PdT, we will address three major research problems: (a) the development of long-term residential systems, which gave rise to a conspicuous Intermediate Depression or pampa socio-ecological system, (b) the emergence of the PdT as a glacial refuge during the last glacial-interglacial transition; and (c) the coevolution and interdependence of the natural and cultural systems that ended with the disappearance of the pampa socio-ecological system and concomitant sequential extinction and extirpation of its biodiversity. The corollary of this process was that at the beginning of the Holocene, when the availability of water became insufficient, an exodus took place that must have had profound consequences for these groups, who had to abandon this landscape that they co-created for almost 2,000 years. Consequently, unlike the Andes or the Pacific coast, this early socio-ecological system did not continue into the Holocene. The lack of high quality and publicly available archaeological, paleoecological and paleontological datasets has weakened the general theoretical debate on early human migrations, settlement and the development of local socio-ecological systems. Here, we conceive human societies as part of the natural ecosystems on which they depend for their subsistence using a socio-ecological approach to analyze and understand the relationship and mutual influence between humans and what we consider nature today. This does not mean that early hunter-gatherers did not exploit or overexploit natural resources, but that they viewed them as social beings and heavily sanction overexploitation when it occurs or try to avoid it, for example through the implementation of taboos. Our project proposes the novel hypothesis that the Intermediate Depression offered sufficient conditions and resources for the development of a residential system and a unique pampa cultural tradition. Our view contrasts with the idea that the settlement pattern of the terminal Pleistocene hunter-gatherers would have been highly mobile and short-lived. The second novelty of this research is the composite methodology, that integrates different disciplinary methods such as: stable isotope analyses including Sr (to search for regional human mobility); paleogenomics to improve the resolution of morphological bone and plant taxa determination; geochronological dating, involving OSL and U/Th techniques to expand our chronologies; and technomorphological characterization of lithic, bone, wooden and textile artifacts, through complete chaîne opératoire methodology, pedological studies for soil horizon description. In sum, our major goal is to understand a different migration route and settlement system for the early peopling of the western slope of the Andes, by defining and explaining the characteristics of the residential systems developed in the PdT during the Pleistocene-Holocene transition, and the local ecologies associated to them. Our data will contribute towards resolving an old problem: the colonization of South America through the study of what is likely one of the best preserved and mostly unaltered sets of early American sites in all South America.

La región de O´Higgins, cuya principal actividad económica corresponde a la agricultura, está siendo severamente afectada por la sequía como consecuencia del cambio climático, generando impactos negativos para este sector productivo . Así, la búsqueda de especies y/o cultivares con mayor tolerancia al estrés hídrico es clave para diversificar l a matriz productiva de la región. El almendro es una opción viable para la región debido a su ampliamente reportada tolerancia al estrés hídrico, con gran éxito en el cultivo de esta especie en áreas con clima Mediterráneo, incluyendo Chile, por lo que la identificación de cultivares con mayor tolerancia a este estrés es de importancia. A nivel fisiológico, el principal efecto del estrés hídrico es el cierre estomático, con el objetivo de evitar una disminución drástica en el estado hídrico de la planta (p otencial hídrico, Ψ L ), esto disminuye la asimilación de carbono y por consiguiente la producción. Sin embargo, especies y cultivares han desarrollado distintas estrategias para responder frente al estrés hídrico, lo que se ha descrito a través de los compo rtamientos isohídricos y anisohídricos. En breve, especies/cultivares con comportamiento isohídrico se caracterizan por un rápido cierre estomático frente al estrés hídrico previniendo así caídas drásticas en Ψ L . Por el contrario, especies/cultivares aniso hídricos mantienen la apertura estomática durante el estrés, permitiendo una caída en Ψ L y, por lo tanto, sosteniendo la asimilación de carbono. En consecuencia, el comportamiento anisohídrico se asocia a mayores tasas fotosintéticas y eficiencia de uso de agua a pesar de la escasez hídrica. La caracterización e identificación de genotipos anisohídricos es importante para optimizar la búsqueda de nuevos cultivares a ser producidos en la región de O´Higgins, especialmente en el secano interior donde los efec tos del déficit hídrico son más severos. Como parte del desarrollo del proyecto Fondecyt de iniciación de la Dra. Alvarez, se han identificado y caracterizado a nivel fisiológico tres cultivares de almendro con comportamiento an/isohídricos contrastantes: Avijor, Isabelona y Soleta. Si bien el proyecto anteriormente descrito incluye el análisis transcripcional de algunos genes, que hipotéticamente tendrían un rol en la diferenciación entre ambos comportamientos, este análisis puntual no permitiría comprende r en profundidad los mecanismos moleculares y rutas que subyacen procesos adaptativos y respuestas a señales ambientales a nivel de genoma completo. Para ahondar en esto último, hemos planteado el siguiente objetivo general: “ Determinar las diferencias gen ómicas, epigenéticas y transcriptómicas que determinan el fenotipo anisohídrico e isohídrico entre distintos cultivares de almendro durante el estrés de déficit hídrico” hídrico”. Sin embargo, a la fecha solamente tres variedades de almendro han sido secuenciadas : Nonpareil, Texas y Lauranne. Si bien el genoma de esta especie es pequeño (~250Mb) su alto nivel de heterocigosidad dificulta su ensamble. Específicamente para esta especie, abordaremos la secuenciación del genoma con una estrategia híbrida que integra d atos de Oxford Nanopore (para secuencias largas) y MGI (lecturas cortas) y algoritmos desarrollados por el Dr. Di Genova que permitirán realizar construcciones a escala cromosómica para las tres variedades propuestas. Los genomas ensamblados permitirán det erminar variantes genéticas y patrones epigenéticos diferenciales entre los tres cultivares propuestos. Adicionalmente, secuenciaremos y analizaremos datos de expresión génica de las tres variedades enfrentadas a estrés hídrico, lo que nos permitirá estudi ar por primera vez el impacto funcional de variantes genéticas y epigenéticas asociados al estrés hídrico. En resumen, nuestro proyecto multidisciplinario generará el genoma de referencia y epigenoma para los tres cultivares: Avijor, Isabelona y Soleta. A dicionalmente, realizaremos un primer mapeo a nivel genómico, epigenético y de expresión de los mecanismos y programas moleculares durante el estrés hídrico de los tres cultivares de almendro.

El cáncer es la segunda causa de muerte en la población Chilena y se proyecta que en diez años será la primera causa de muerte en el país. A nivel regional, la región de O Higgins es la que presenta la mayor incidencia de muertes por cáncer. Actualmente, Chile invierte alrededor del 1% del PIB en atención y tratamiento del cáncer. Es indispensable y urgente comenzar a caracterizar molecularmente los cánceres prevalentes de la población Chilena pues esto permitirá integrar información que impactará las decisiones clínicas permitiendo la implementación de tratamientos específicos para los pacientes. El estudio genómico y molecular de sistemas biológicos complejos, como el desarrollo y progresión del cáncer, requieren del desarrollo de nuevos algoritmos y modelos teóricos para analizar e interpretar datos genómicos complejos (big- data). El principal objetivo del laboratorio de genómica computacional que instalaré en el instituto de ciencias de la ingeniería de la Universidad de O Higgins será desarrollar investigación de vanguardia entorno al diseño y aplicación de nuevos algoritmos y tecnologías ómicas para estudiar la arquitectura genómica de cánceres prevalentes de la población Chilena. La meta a largo plazo es trasladar estas tecnologías a la práctica clínica e impulsar la implementación de programas de medicina de precisión enfocados en el tratamiento y prevención del cáncer en nuestro país y región. Un segundo objetivo es impulsar y liderar investigación multidisciplinaria en temáticas de salud, agroindustria y minería, sectores críticos a desarrollar en la región de O'Higgins. Finalmente, el laboratorio de genómica computacional contribuirá a la formación de capital humano avanzado en áreas asociadas a la genómica, bioinformática y biología computacional.

The Chilean government recently launched the national cancer plan to increase survival rates and reduce cancer incidence, which is projected to become the first cause of death in the Chilean population. Only in 2020, more than 55,000 new cases of cancer were registered. Therefore, starting the molecular characterization of the prevalent cancers of the Chilean population is urgent since this can inform therapeutic decisions and thus promote more specific treatments for patients, positively impacting survival rates and prevention. Due to the constant improvement of sequencing technologies, cancer research increasingly relies on the interpretation and analysis of high-dimensional genomic data. Genomic cancer analysis has revealed that the mutation repertoire of tumors is vast and goes from single nucleotide variants to whole-genome duplications. Structural variants (SVs) and copy number alterations are significant drivers of cancer proliferation and represent the building blocks of complex mutational processes involving the rearrangement of large genomic regions. These complex genomic rearrangements have functional consequences (e.g., gene fusion formation, inactivation of tumor suppressor) and have been associated with lower survival and poor response to immunotherapy. The patterns of small somatic variants have been well studied and characterized in human cancers. However, the genetic architecture and functional consequences of complex genomic rearrangements, despite their clinical significance, still need to be explored due to algorithmic and technological limitations. Therefore, the aims of this proposal are first to develop novel computational tools to fully characterize the genetic architecture of complex genomic rearrangements and second to study their functional impact on tumor gene expression programs through the lens of a solid theoretical framework. Methodologically, the de novo assembly of genomes is the only approach that allows a complete and unbiased characterization of all genomic alterations. Recently, we developed WENGAN, a new algorithm for the ultrafast, accurate, and complete de novo reconstruction of human genomes combining short and long reads technologies. Initial validation of WENGAN for de novo reconstruction of cancer genomes enabled the discovery of a large degree of tumor genomic reorganization with thousands of SVs. The latter remains elusive when using alternative algorithms and technologies. Therefore, this experience represents a solid foundation for developing this proposal. We will work with the following specific objectives: 1) Develop efficient algorithms to reconstruct haplotype-resolved genomes; 2) combine haplotype-resolved genomes and variation graphs with building complete structural variant maps of tumors; 3) study the functional impact of complex SVs at the single-cell level; and 4) Infer from multi-omic data the tumor tasks (trade-offs) using the multi-task evolution theory. We have assembled a multidisciplinary network of national and international (France and Germany) experts in algorithms, sequencing technologies, and cancer genomics to develop these objectives. Additionally, we compromise the mentoring and training of undergraduate and magister students by offering thesis topics directly related to the proposal's goals. In summary, we propose an approach that integrates the development of new computational algorithms, a solid theoretical framework, and the generation of state-of-the-art multi-omic data to study the genetic architecture and functional impact of large-scale genomic rearrangements in a prevalent Chilean cancer. The project will deliver, in four years, the first haplotype-resolved Chilean genome, the first graph reference of Chilean individuals, and the first multi-omic characterization of a prevalent Chilean cancer.

Listeria monocytogenes (Lm) is a foodborne pathogen that causes listeriosis, a severe invasive disease, with mortality rates as high as 30 %. This pathogen has caused several foodborne outbreaks and product recalls worldwide, with significant economic consequences for the food industry. Lm can resist many stresses used in food-processing environments (FPE) to control bacterial growth. Biofilm formation is another strategy that allows Lm to persist in FPE and contaminate foods. In natural environments, biofilms often consist of mixedspecies communities with dynamic interactions between different species. The structure and persistence of these biofilms are determined by community compositions, cooperative development, genomic background, environment-responsive gene expression, and the material on which the biofilm forms, among others. The design of materials with anti-bacterial and anti-biofilm properties is an emerging strategy to control the presence of foodborne pathogens in the FPE. Smart surfaces with on-demand antimicrobial protection through “physical” activation are ideal for this application. For instance, conductive polymers and piezocatalytic materials generate reactive oxygen species (ROS) by photothermal or mechanical stimulus, respectively. To further advance in the design of effective ROS-releasing antibiofilm materials, it is essential to understand the microbial interactions occurring in biofilms and how molecular mechanisms are regulated by the pathogen under ROS-based stress conditions. In this study, we hypothesize that “The efficacy of ROSreleasing antibiofilm materials can be modulated based on knowledge of the interactions between Lm isolates and other species on biofilms formed under FPE simulated conditions and by identifying specific molecular mechanisms regulated by Lm isolates that persist under these environmental conditions.” This research will take an interdisciplinary approach, integrating knowledge from different fields (microbiology, molecular biology, chemistry, and materials science) to better understand the mechanisms involved in Lm biofilm formation under FPE conditions and use this information to design efficient materials to control bacterial contamination. Our main aim is “to investigate the interplay between Lm and other bacteria in ROS-releasing antibiofilm materials under FPE conditions and identify the molecular mechanisms that Lm activates.” Specific aim-1 To define the best condition for tailor-made ROS generation in conductive polymers and polymer/ZnO composites able to control Lm mixed biofilms. We will design and assess the ROS generation capabilities of conductive polypyrrole (PPy) and piezocatalytic polymer/ZnO materials. We currently have a collection of 300 Lm strains isolated from various sources. Approximately 50% of these strains have had their whole genomes sequenced. The effect of ROS-releasing materials on cell adhesion and biofilm formation will be tested for Lm strains in the presence of other bacterial species isolated from FPE (mixed biofilm) at 8ºC. We will identify the best technical conditions of the ROS-releasing material to control or reduce Lm biofilm formation. In addition, we will know if the Lm strains have different levels of tolerance to ROS under the conditions that we will test. Specific aim-2: To identify Lm genetic features associated with tolerance on ROS-releasing materials. Additional Lm strains from our collection will be sequenced. We will also have access to Lm strains isolated from listeriosis outbreaks with their genome sequences. We will analyze the genomes of Lm strains exhibiting varying levels of biofilm tolerance on ROS-releasing materials under FPE conditions. We will evaluate the association between genomic elements (virulence genes, resistance determinants, and other genomic variations) and the tolerance levels of the ROS-releasing materials to identify new genomic elements associated with biofilm formation. Specific aim-3: To identify molecular programs and ecological roles activated by Lm in response to ROS-releasing material under FPE conditions One material with adjusted photothermal and mechanical ROS generation will be selected to evaluate the global transcriptional response of Lm isolates able to tolerate ROS-releasing materials. We will evaluate this response considering FPE conditions: low temperature and mixed biofilms. In this way, we will identify if some Lm isolates activate specific molecular mechanisms that are associated with the persistence/or higher tolerance to ROS-releasing materials under FPE conditions. Expected outcomes: This research will contribute to advancing the antibiofilm material design, understanding Lm genetic characteristics, and identifying molecular mechanisms activated under conditions used in food processing areas, thus promoting improved food safety and industry practices.

Center for Mathematical Modeling.

El cáncer es una enfermedad genética compleja y mortal que afecta a un gran número de personas en Chile, con una alta tasa de mortalidad y un aumento constante en el número de casos. Ante esta realidad, es crucial implementar la Medicina de Precisión en el país para brindar un tratamiento personalizado y mejorar los resultados para los pacientes. El Centro UOH de BioIngeniería (CUBI) se propone liderar este avance, enfocándose en la región de O'Higgins, Chile. El CUBI busca crear mapas moleculares multiómicos de los cánceres prevalentes en la región, utilizando tecnologías de vanguardia y algoritmos avanzados. Esto permitirá comprender los perfiles genéticos y moleculares del cáncer, así como la heterogeneidad y evolución somática de los tumores chilenos. El equipo propuesto por CUBI, con su destacada capacidad de secuenciación genómica, procesamiento masivo de datos y experiencia en biología molecular y computacional, desempeñará un papel protagónico en el logro de estos objetivos. El CUBI se organiza en tres líneas de investigación principales. La primera línea se centra en las tecnologías genómicas para el mapeo de genotipos, fenotipos y evolución tumoral, dirigida por el Dr. Di Genova. Su objetivo es comprender los factores genéticos que contribuyen al cáncer, así como la variabilidad molecular y la evolución somática de los tumores chilenos. La segunda línea, liderada por el doctor Henao, se enfoca en las tecnologías de imagen para el mapeo y evaluación de fenotipos tumorales. Mediante el uso de imágenes histológicas y de ultrasonido, combinadas con la inteligencia artificial y modelos físico/matemáticos, se busca identificar patrones morfológicos y topológicos asociados a biomarcadores o procesos mutacionales específicos de los tumores. La tercera línea de investigación, liderada por el Dr. Krause, se centra en la utilización de modelos preclínicos para validar las relaciones fenotipo-genotipo desCUBIertas en las líneas de investigación anteriores y la creación de un biobanco regional. Esto permitirá realizar estudios moleculares, clínicos y epidemiológicos en la región de O'Higgins, fortaleciendo la base de conocimientos y facilitando la aplicación de los hallazgos en la práctica clínica. El CUBI cuenta con un equipo interdisciplinario de investigadores jóvenes, intermedios y senior, con líneas de investigación claras y bien definidas. Además, se ha establecido una sólida red nacional e internacional de colaboración con instituciones líderes en investigación del cáncer, como el IARC de Lyon, Francia, el ICR de Londres, UK y hospitales e instituciones en Chile. El CUBI busca posicionarse como un centro pionero en la investigación en medicina de precisión oncológica en Chile. Su objetivo principal es comprender y mapear la biología única de los pacientes chilenos/as con cáncer, con el fin de brindar tratamientos más efectivos y mejorar las oportunidades para la región. Con su infraestructura, equipo, red de colaboración y enfoque multidisciplinario, el CUBI tiene el potencial de generar un impacto significativo en la sociedad chilena al avanzar en la comprensión del cáncer y la implementación de estrategias de tratamiento personalizado. Proyectamos que la operación del CUBI tendrá un impacto positivo en la región y país en varios aspectos: 1. Mejorar la atención del cáncer: El CUBI permitirá una mejor comprensión de las características genéticas y moleculares de los tumores en la población regional y nacional. Esto conducirá a un diagnóstico más preciso, una estratificación más efectiva de los pacientes y una selección más precisa de los tratamientos. Como resultado, los pacientes recibirán terapias más efectivas, lo que mejorará sus resultados clínicos y su calidad de vida. 2. Avances científicos y tecnológicos: El centro promoverá el desarrollo y la aplicación de tecnologías de vanguardia y métodos de análisis de datos avanzados. Esto fomentará la investigación científica del cáncer y permitirá descubrir nuevas asociaciones genéticas y moleculares, así como identificar posibles blancos terapéuticos. Estos avances no solo beneficiarán a los pacientes de cáncer en Chile, sino que también contribuirán al conocimiento global en la lucha contra esta enfermedad. 3. Formación y educación: El centro brindará oportunidades de formación y capacitación para estudiantes, investigadores y profesionales de la salud interesados en la medicina de precisión en oncología. Esto fortalecerá la capacidad científica y clínica de la región, permitiendo la formación de especialistas altamente calificados en el diagnóstico y tratamiento del cáncer. 4. Impacto socioeconómico: La detección temprana, el tratamiento personalizado y la reducción de los efectos secundarios innecesarios pueden mejorar la eficiencia de los sistemas de salud y disminuir los costos asociados con el cáncer. Además, la generación de conocimiento científico y tecnológico puede impulsar la innovación y el desarrollo de la industria biotecnológica en la región, creando oportunidades económicas y empleo especializado. En resumen, el CUBI tiene el potencial de generar un impacto significativo en la sociedad regional al mejorar la atención médica, impulsar la investigación científica, fortalecer la capacitación y la colaboración, y tener repercusiones socioeconómicas positivas. Al comprender y abordar la complejidad biológica del cáncer en la población chilena, se allana el camino para una atención más efectiva y personalizada, y se brinda esperanza a los pacientes y sus familias en la lucha contra el cáncer.

Proyecto interno de la UOH de carácter multidisciplinario que busca crear mapas moleculares multiómicos de los cánceres prevalentes en la región, utilizando tecnologías de vanguardia y algoritmos avanzados.

TRANSFERENCIA SUPERCOMPUTACIÓN PARA INNOVACIÓN EN SALUD REGIONAL: HPC-UOH Y HRLBO

Chile is facing one of the steepest increases in Colorectal cancer (CRC) incidence and mortality in the Southern Cone, with the greatest surge occurring in adults ≤ 50 years. Incidence is lowest in the far north and increases toward the south-central regions, mirroring a gradient in Aymara-Mapuche Native-American ancestry, an axis largely absent from the European reference cohorts that guide modern precision oncology. To fill this gap, we propose a four-year project to create the first Chile-specific, multi-omic and histopathological atlas of CRC and to explore ancestry-aware, AI-assisted diagnostics. Rationale and Hypothesis. We hypothesise that Chilean CRC shows (i) unique, ancestry-driven molecular patterns that differ from European tumors; (ii) AI models can detect these patterns directly on routine whole-slide images, and (iii) they shape distinct evolutionary paths in early- versus late-onset disease. Specific objectives. Molecular landscape & heterogeneity: Produce single-gland long-read WGS, methylome, and transcriptome profiles for 100 tumors (30 early-onset, 70 late-onset; ≥30× coverage, ≥50 % purity). Ancestry impact: Phase somatic alterations by local ancestry and contrast their frequencies with European CRC genomes (TCGA, PCAWG). AI-enhanced histopathology: Train and externally validate multi-instance-learning (MIL) models that predict microsatellite instability, driver mutations, and whole-genome doubling from matched WSIs, targeting AUC ≥ 0.80 (pilot: AUC ≥ 0.85 for whole-genome doubling on TCGA WSIs). Evolutionary trajectories: Multi-region sequence early-onset and late-onset tumors, reconstruct their clonal phylogenies, and contrast the resulting evolutionary patterns between the two age groups. Team capacity & resources. Computational biologist Alex Di Genova (genomics & AI), pathologist Juan Carlos Araya (digital pathology), and gastro-immunologist Tamara Pérez-Jeldres (clinical phenotyping) have prospective access to >220 new CRC resections and >1,800 registry entries each year. A biobank already houses 100 well-annotated tumour specimens from hospitals in Santiago and the O’Higgins Region, ready for immediate sequencing and imaging. As a team we are delivering important results as (i) the generation of the first telomere-to-telomere Chilean genome, establishing a population-specific reference; (ii) sequenced >270 high-coverage whole genomes of chileans individuals (70 healthy donors, 120 hereditary-breast-cancer cases, 80 primary gallbladder tumors); iii) built the first multi-omic atlas of gallbladder cancer by integrating our data with Korean (n = 94) and Indian (n = 64) cohorts, uncovering a Chile-enriched proliferative phenotype; and (iv) developed CRAB-MIL, a weakly supervised deep-learning framework that predicts whole-genome doubling from routine H&E slides with an AUC > 0.85 and provides attention maps for interpretability. These accomplishments demonstrate our ability to generate, integrate, and clinically interpret large-scale genomic and AI datasets—capabilities directly transferable to Chilean CRC. International collaborators Anaïs Baudot (Marseille) and Luis Zapata (Institute of Cancer Research, London) further contribute multi-omic network analysis and evolutionary-genomics expertise, respectively. Interdisciplinary workflow. Clinical phenotyping, computational histopathology, PromethION sequencing, and Nextflow harmonisation feed ancestry-aware genomic analyses; attention-based models are fine-tuned on TCGA and Chilean WSIs; computational, pathology, and gastroenterology teams jointly review outputs to prioritise clinically relevant signals. All variant calls, methylomes, expression matrices, AI prediction, and metadata will be released through an open and intuitive TumorMap portal. Expected Outcomes and Impact. The project will (i) reveal population-specific drivers and mutational processes, (ii) quantify the frequency of clinically actionable biomarkers originally identified in Europeans, (iii) deliver image-based tools that offer low-cost, molecular stratification and heterogeneity scoring, and (iv) provide a high-resolution evolutionary framework for EO versus LO CRC. Collectively, these data will offer the first high-resolution portrait of the Chilean CRC and lay the groundwork for ancestry-aware screening, diagnostic, and treatment strategies.