Genome-wide microarray technology has facilitated the systematic discovery of diagnostic biomarkers of cancers and other pathologies. However, meta-analyses of published arrays using melanoma as a test cancer has uncovered significant inconsistences that hinder advances in clinical practice. In this study a computational model for the integrated analysis of microarray datasets is proposed in order to provide a robust ranking of genes in terms of their relative significance; both genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). When applied to five melanoma microarray datasets published between 2000 and 2011, a new 12-gene diagnostic biomarker signature for melanoma was defined (i.e., EGFR, FGFR2, FGFR3, IL8, PTPRF, TNC, CXCL13, COL11A1, CHP2, SHC4, PPP2R2C, and WNT4). Of these, CXCL13, COL11A1, PTPRF and SHC4 are components of the MAPK pathway and were validated by immunocyto- and immunohisto-chemistry. These proteins were found to be overexpressed in metastatic and primary melanoma cells in vitro and in melanoma tissue in situ compared to melanocytes cultured from healthy skin epidermis and normal healthy human skin. One challenge for the integrated analysis of microarray data is that the microarray data are produced using different platforms and bio-samples, e.g. including both cell line- and biopsy-based microarray datasets. In order to address these challenges, the computational model was further enhanced the stratification of datasets into either biopsy or cell line derived datasets, and via the weighting of microarray data based on quality criteria of data. The methods enhancement was applied to 14 microarray datasets of three cancers (breast, prostate, and melanoma) based on classification accuracy and on the capability to identify predictive biomarkers. Four novel measures for evaluating the capability to identify predictive biomarkers are proposed: (1) classifying independent testing data using wrapper feature selection with machine leaning, (2) assessing the number of common genes with the genes retrieved in independent testing data, (3) assessing the number of common genes with the genes retrieved in across multiple training datasets, (4) assessing the number of common genes with the genes validated in the literature. This enhancement of computational approach (i) achieved reliable classification performance across multiple datasets, (ii) recognized more significant genes into the top-ranked genes as compared to the genes detected by the independent test data, and (iii) detected more meaningful genes than were validated in previous melanoma studies in the literature.

Genome-wide microarray technology has facilitated the systematic discovery of diagnostic biomarkers of cancers and other pathologies. However, meta-analyses of published arrays using melanoma as a test cancer has uncovered significant inconsistences that hinder advances in clinical practice. In this study a computational model for the integrated analysis of microarray datasets is proposed in order to provide a robust ranking of genes in terms of their relative significance; both genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). When applied to five melanoma microarray datasets published between 2000 and 2011, a new 12-gene diagnostic biomarker signature for melanoma was defined (i.e., EGFR, FGFR2, FGFR3, IL8, PTPRF, TNC, CXCL13, COL11A1, CHP2, SHC4, PPP2R2C, and WNT4). Of these, CXCL13, COL11A1, PTPRF and SHC4 are components of the MAPK pathway and were validated by immunocyto- and immunohisto-chemistry. These proteins were found to be overexpressed in metastatic and primary melanoma cells in vitro and in melanoma tissue in situ compared to melanocytes cultured from healthy skin epidermis and normal healthy human skin. One challenge for the integrated analysis of microarray data is that the microarray data are produced using different platforms and bio-samples, e.g. including both cell line- and biopsy-based microarray datasets. In order to address these challenges, the computational model was further enhanced the stratification of datasets into either biopsy or cell line derived datasets, and via the weighting of microarray data based on quality criteria of data. The methods enhancement was applied to 14 microarray datasets of three cancers (breast, prostate, and melanoma) based on classification accuracy and on the capability to identify predictive biomarkers. Four novel measures for evaluating the capability to identify predictive biomarkers are proposed: (1) classifying independent testing data using wrapper feature selection with machine leaning, (2) assessing the number of common genes with the genes retrieved in independent testing data, (3) assessing the number of common genes with the genes retrieved in across multiple training datasets, (4) assessing the number of common genes with the genes validated in the literature. This enhancement of computational approach (i) achieved reliable classification performance across multiple datasets, (ii) recognized more significant genes into the top-ranked genes as compared to the genes detected by the independent test data, and (iii) detected more meaningful genes than were validated in previous melanoma studies in the literature.

<p>The accumulation of high-throughput data from vast sources has drawn a lot attentions to develop methods for extracting meaningful information out of the massive data. More interesting questions arise from how to combine the disparate information, which goes beyond modeling sparsity and dimension reduction. This dissertation focuses on the innovations in the area of heterogeneous data integration.</p><p>Chapter 1 contextualizes this dissertation by introducing different aspects of meta-analysis and model frameworks for high-dimensional genomic data.</p><p>Chapter 2 introduces a novel technique, joint Bayesian sparse factor analysis model, to vertically integrate multi-dimensional genomic data from different platforms. </p><p>Chapter 3 extends the above model to a nonparametric Bayes formula. It directly infers number of factors from a model-based approach.</p><p>On the other hand, chapter 4 deals with horizontal integration of diverse gene expression data; the model infers pathway activities across various experimental conditions. </p><p>All the methods mentioned above are demonstrated in both simulation studies and real data applications in chapters 2-4.</p><p>Finally, chapter 5 summarizes the dissertation and discusses future directions.</p> / Dissertation

O presente trabalho é um estudo de Geomorfologia aplicada com o objetivo de analisar, de forma integrada, um ambiente urbanizado, em uma sub-bacia do manancial da Guarapiranga, na cidade de São Paulo. O enfoque é o diagnóstico da Fragilidade Ambiental e sua correlação com o Índice Paulista de Vulnerabilidade Social (IPVS Fundação SEADE). Para isso, foi elaborado um mapeamento geomorfológico, em escala de detalhe - como suporte para o entendimento da dinâmica dos processos morfológicos - e o mapa de uso e cobertura da superfície da Terra, que expressa as concretudes das ações antrópicas e a conjuntura de flora presente na área, para obtenção de informações sobre a proteção da superfície contra intemperismos. Em seguida foi feita uma intersecção entre estes dois mapas e foi elaborado o mapa de Fragilidade Ambiental. Em um segundo momento, foi feito um mapa com a espacialização SEADE do Índice Paulista de Vulnerabilidade Social, para representar os dados socioeconômicos especializados conforme setores censitários. Por fim, foi elaborada uma correlação entre os mapas de Vulnerabilidade Social e Fragilidade Ambiental. Com isso, foi possível demonstrar que as áreas de vulnerabilidades mais altas foram assentadas em terrenos de fragilidade forte e muito forte e que as áreas precisam de cuidados específicos para a devida ocupação. / The present work is a study of Applied Geomorphology, with the aim of analyze, in an integrated manner, an urban environment in a sub-basin of the water reservoir of Guarapiranga, in the city of São Paulo, Brazil. The focus is the diagnosis of Environmental Fragility and its correlation with Paulista Social Vulnerability Index (IPVS Foundation SEADE). For this, a geomorphological mapping was developed in detail scale - as support for understanding the dynamics of morphological processes - and the land cover mapping, which expresses the materiality of human activities and the vegetation distribution in the landscape, this mapping provides informations about how much the cover protects the ground surface against climate effects. Then was made an intersection between these two maps and the map of Environmental Fragility was prepared. In a second step, a map showing the spatial distribution of the Paulista Social Vulnerability Index (SEADE), was made to represent the specialized socioeconomic data. Finally, a correlation was drawn between the maps of Social Vulnerability and Environmental Fragility. Thus, it was possible to demonstrate that the areas of highest vulnerability were settled in the strong and very strong and fragile land areas that need special care to occupation.

O presente trabalho é um estudo de Geomorfologia aplicada com o objetivo de analisar, de forma integrada, um ambiente urbanizado, em uma sub-bacia do manancial da Guarapiranga, na cidade de São Paulo. O enfoque é o diagnóstico da Fragilidade Ambiental e sua correlação com o Índice Paulista de Vulnerabilidade Social (IPVS Fundação SEADE). Para isso, foi elaborado um mapeamento geomorfológico, em escala de detalhe - como suporte para o entendimento da dinâmica dos processos morfológicos - e o mapa de uso e cobertura da superfície da Terra, que expressa as concretudes das ações antrópicas e a conjuntura de flora presente na área, para obtenção de informações sobre a proteção da superfície contra intemperismos. Em seguida foi feita uma intersecção entre estes dois mapas e foi elaborado o mapa de Fragilidade Ambiental. Em um segundo momento, foi feito um mapa com a espacialização SEADE do Índice Paulista de Vulnerabilidade Social, para representar os dados socioeconômicos especializados conforme setores censitários. Por fim, foi elaborada uma correlação entre os mapas de Vulnerabilidade Social e Fragilidade Ambiental. Com isso, foi possível demonstrar que as áreas de vulnerabilidades mais altas foram assentadas em terrenos de fragilidade forte e muito forte e que as áreas precisam de cuidados específicos para a devida ocupação. / The present work is a study of Applied Geomorphology, with the aim of analyze, in an integrated manner, an urban environment in a sub-basin of the water reservoir of Guarapiranga, in the city of São Paulo, Brazil. The focus is the diagnosis of Environmental Fragility and its correlation with Paulista Social Vulnerability Index (IPVS Foundation SEADE). For this, a geomorphological mapping was developed in detail scale - as support for understanding the dynamics of morphological processes - and the land cover mapping, which expresses the materiality of human activities and the vegetation distribution in the landscape, this mapping provides informations about how much the cover protects the ground surface against climate effects. Then was made an intersection between these two maps and the map of Environmental Fragility was prepared. In a second step, a map showing the spatial distribution of the Paulista Social Vulnerability Index (SEADE), was made to represent the specialized socioeconomic data. Finally, a correlation was drawn between the maps of Social Vulnerability and Environmental Fragility. Thus, it was possible to demonstrate that the areas of highest vulnerability were settled in the strong and very strong and fragile land areas that need special care to occupation.

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No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Rosilene Fileti.pdf: 10367368 bytes, checksum: 9ba1c33c57b55bb71dfe9f14ca41c531 (MD5) / FAPES / Esta pesquisa associa os processos morfodinâmicos vigentes ao comportamento mecânico de um Latossolo Vermelho-Amarelo de gnaisse, de uma vertente policonvexa situada no distrito de São João de Viçosa, município de Venda Nova do Imigrante – ES. Considerando a incidência de movimentos de massa, a literatura classifica os Latossolos como estáveis, contudo, na área de estudo foram constatadas evidências de escorregamento translacional. A investigação das causas desse evento foi baseada em análises geomorfológicas e na interpretação de resultados de ensaios físico-mecânicos do solo. Para compreender a dinâmica do fluxo superficial e a relação com os movimentos de material das vertentes que compõem a área de estudo, gerou-se um produto cartográfico que corresponde a uma compartimentação geomorfológica da área. Esse, por sua vez, subsidiou a proposta de análise integrada do relevo que fundamenta metodologicamente essa pesquisa. A partir da investigação de três níveis distintos de abordagem, Compartimentação Topográfica, Estrutura Superficial da Paisagem e Fisiologia da Paisagem, procurou-se estabelecer as relações de causa e efeito que os eventos pluviométricos, o comportamento da água no solo e as ações antrópicas exercem sobre a área estudada, o que permitiu avaliar a estabilidade da vertente. A magnitude-frequência dos eventos pluviométricos indicou que chuvas de 17, 21 mm são as mais recorrentes na área de estudo durante o ano e preparam o solo para entrada de água. Para compreender o comportamento hídrico-mecânico do solo, foram realizados os seguintes ensaios: caracterização do solo (limites de Atterberg, densidade real dos grãos, teor de matéria orgânica), análises físicas acerca de granulometria, porosidade total, macroporosidade e microporosidade, condutividade hidráulica, argila dispersa em água, densidade do solo e ensaio de cisalhamento direto. As curvas de retenção de água no solo refletiram um comportamento de solo argiloso para as profundidades amostradas do horizonte BW1 investigadas e a integração dos resultados permitiu constatar uma descontinuidade hidráulica a 1,5m de profundidade nesse horizonte. Os resultados indicaram ainda que a textura, estrutura e porosidade do Latossolo amostrado influenciam, em grande parte, na resistência ao cisalhamento. Por meio do ensaio de cisalhamento direto obtiveramse os valores de ângulo de atrito e coesão para os horizontes BW1, 27,69º e 0,12kgf/cm2 e C, 32,82º e 0,05kgf/cm2 e estes, por sua vez, foram utilizados como parâmetros na análise de estabilidade no software Slope/W™. Concluiu-se, portanto, que as alterações na dinâmica natural da vertente em decorrência do uso e da abertura de cortes para ampliação de vias e da ocupação, têm relação direta com a instabilização do solo. / This dissertation associates the morphodynamic processes current to the mechanical behavior of a residual Oxisol of gneiss, a policonvexa slope located in São João de Viçosa, district of municipality Venda Nova do Imigrante - ES. Considering the incidence of mass movements, the literature classifies Oxisol like stable. However, in the study area were ascertained evidence slip translational. The investigation into the causes of this event was based on geomorphological analysis and in the interpretation of test results aimed at soil mechanics. To understand the dynamic of the surface flow and its relationship with material movement the slope, it was generated a cartographic product which corresponds to the geomorphology of the area partitioning. This in turn, supported the proposal the analysis integrated of relief methodologically grounded this research. From the investigation of three different levels of approach, Compartmentalization Topographic, Surface Structure of Landscape and Landscape Physiology, tried to establish relations of cause and effect that pluviometric events, water behavior in soil and human activities exert on the study area, which allowed evaluating the stability of the slope. The magnitudefrequency rainfall events indicated that rainfall of 17, 21 mm are the most frequent in the study area during the year and prepare the soil for water ingress. To understand the hydro-mechanical behavior of the soil the following tests were performed: characterization of soil (Atterberg limits, actual density of the grains, organic matter content), physical analyzes of particle size, porosity, macroporosity and microporosity, hydraulic conductivity, water dispersed clay, soil bulk density and direct shear test. The water retention curve in the soil reflected a clay soil behavior to the depths sampled the BW1 horizon investigated and the integration of the results allowed establishing a hydraulic discontinuity 1.5m deep in this horizon. The results also indicated that the texture, structure and porosity of the sampled Oxisol influence largely in shear strength. By means of direct shear testing were obtained the angle of friction values for cohesion and BW1 horizons 27,69º; 0,12kgf/cm2 and C 32,82º and 0.05 kgf/cm2 and these in turn were used as parameters in the stability analysis Slope/W ™ software. It was concluded, therefore, that changes in the natural dynamics of the slope due to the use and opening cuts to expand routes and occupation, are directly related to the instability of the ground.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / O avanÃo dos processos de desertificaÃÃo e degradaÃÃo da terra tem se manifestado de forma crescente no semiÃrido brasileiro, muitas vezes ocasionados pela utilizaÃÃo indiscriminada dos recursos naturais, seja para manutenÃÃo do sistema produtivo vigente, ou atà mesmo pela falta de informaÃÃo no manuseio desses recursos. A pesquisa faz uma anÃlise da sub-bacia hidrogrÃfica do Riacho Santa Rocha, localizada no baixo curso do Rio Banabuià cuja Ãrea total à de 675 kmÂ. Como objetivo geral tem-se a anÃlise dos sistemas ambientais da sub-bacia, em carÃter de diagnÃstico, com intuito de estabelecer subsÃdios para futuras intervenÃÃes. A concepÃÃo utilizada para a discussÃo foi pautada nos estudos integrados, com Ãnfase na anÃlise sistÃmica do ambiente. Do ponto de vista metodolÃgico o trabalho foi dividido em seis etapas: anÃlise de material bibliogrÃfico, cartogrÃfico e imagens de satÃlites; produÃÃo de mapas para auxÃlio no campo; trabalhos de campo para a comprovaÃÃo dos dados; correÃÃo e adequaÃÃo do material cartogrÃfico produzido para o contexto da pesquisa; aplicaÃÃo de questionÃrios e dos indicadores geobiofÃsicos de desertificaÃÃo. A partir da metodologia empregada foram delimitados cinco sistemas ambientais: planÃcie ribeirinha e Ãrea de inundaÃÃo sazonal; tabuleiros interiores com coberturas colÃvio-eluviais detrÃticas; sertÃes pediplanados de Morada Nova; sertÃes moderadamente dissecados de Jaguaretama e cristas residuais e inselbergs. Percebeu-se que a utilizaÃÃo dos recursos naturais nÃo à uniforme ao longo da sub-bacia hidrogrÃfica, obedecendo Ãs potencialidades e limitaÃÃes de cada sistema ambiental. Os sistemas ambientais caracterizados pelos sertÃes ainda sÃo as Ãreas mais vulnerÃveis à desertificaÃÃo do ponto de vista geoambiental, ainda mais as Ãreas historicamente utilizadas para a subsistÃncia local. Mesmo com cenÃrios desanimadores, ainda se constatou uma melhora das condiÃÃes de vÃrias comunidades, fruto da melhor acessibilidade aos recursos e dinamicidade econÃmica. Apesar dessa variÃvel positiva, essas Ãreas ainda sÃo esquecidas e desprovidas de assistÃncia por parte do poder pÃblico local. / The advance of desertification and land degradation has manifested increasingly in the Brazilian semiarid region, often caused by the indiscriminate use of natural resources, is to maintain the current production system, or even the lack of information in the management of this resource. The research examined the sub-basin of the creek Santa Rock, located in the lower course of the river and Banabuià with a total area of 675 km Â. As a general objective has been the analysis of the sub-basin environmental systems in diagnostic character, in order to establish a basis for future interventions. The design used for the discussion was based on integrated studies, with emphasis on the systemic analysis of the environment. From the methodological point of view the work was divided into six stages: analysis of publications, cartographic and satellite images; production of maps to help in the field; fieldwork for verification of data; correctness and adequacy of cartographic material produced for the research context and questionnaires. From the methodology used five environmental systems were defined: riverine plain area and seasonal flooding; interior trays with colluvial - eluvial covers detrital; pediplanados hinterlands of New Street; hinterlands moderately dissected Jaguaretama and residual inselbergs and ridges. It was noticed that the use of natural resources is not uniform throughout the sub-basin, according to the potentialities of each environmental system. Environmental systems characterized by hinterland are still the most vulnerable areas from the point of view geoenvironmental, further areas traditionally used for local livelihoods. Even with disappointing scenarios was also found an improvement of the conditions of various communities as a result of better access to resources and economic dynamism. Despite this positive variable, these areas are still neglected and deprived of support by the local government.

Yes / Background: miRNAs (microRNAs) play a key role in triple-negative breast cancer (TNBC) progression, and its heterogeneity at the expression, pathological and clinical levels. Stratification of breast cancer subtypes on the basis of genomics and transcriptomics profiling, along with the known biomarkers’ receptor status, has revealed the existence of subgroups known to have diverse clinical outcomes. Recently, several studies have analysed expression profiles of matched mRNA and miRNA to investigate the underlying heterogeneity of TNBC and the potential role of miRNA as a biomarker within cancers. However, the miRNA-mRNA regulatory network within TNBC has yet to be understood. Results and Findings: We performed model-based integrated analysis of miRNA and mRNA expression profiles on breast cancer, primarily focusing on triple-negative, to identify subtype-specific signatures involved in oncogenic pathways and their potential role in patient survival outcome. Using univariate and multivariate Cox analysis, we identified 25 unique miRNAs associated with the prognosis of overall survival (OS) and distant metastases-free survival (DMFS) with “risky” and “protective” outcomes. The association of these prognostic miRNAs with subtype-specific mRNA genes was established to investigate their potential regulatory role in the canonical pathways using anti-correlation analysis. The analysis showed that miRNAs contribute to the positive regulation of known breast cancer driver genes as well as the activation of respective oncogenic pathway during disease formation. Further analysis on the “risk associated” miRNAs group revealed significant regulation of critical pathways such as cell growth, voltage-gated ion channel function, ion transport and cell-to-cell signalling. Conclusion: The study findings provide new insights into the potential role of miRNAs in TNBC disease progression through the activation of key oncogenic pathways. The results showed previously unreported subtype-specific prognostic miRNAs associated with clinical outcome that may be used for further clinical evaluation. / EPSRC (EP/R043787/1).

O estudo integrado da paisagem permite a verificação dos níveis de interconexão, da estrutura e da funcionalidade de diversas porções da superfície terrestre. Sob este aspecto muitas pesquisas têm incluído como temática, o estudo dos mecanismos de funcionamento da paisagem e a interação entre os seus componentes. Desta forma, torna-se essencial para a ampliação das investigações, a introdução de metodologias e novas técnicas, que inseridas adequadamente, contribuem para o melhor entendimento dos elementos que compõem a paisagem. Neste sentido, este trabalho teve como objetivo identificar, interpretar e compreender a diversidade de fisionomias da paisagem e sua fisiologia, na bacia hidrográfica do rio Botucaraí, Rio Grande do Sul, a partir da aplicação de técnicas de Sensoriamento Remoto, especificamente a Análise por Componentes Principais (ACP). Nesta perspectiva, entende-se que o tratamento das bandas espectrais, a partir de imagens de satélite, configura-se em uma complementação no estudo e no entendimento dos elementos constituintes da paisagem: solos, relevo, litologia e vegetação, além de gerar produtos cartográficos com níveis de detalhamento mais precisos. A técnica de ACP foi aplicada a partir do mapeamento de uso e cobertura da terra, do mapa do relevo, dos mapas temáticos básicos (hipsometria e declividades), do mapa geológico, do mapa da cobertura vegetal e do mapa de solos. Assim, geraram-se as imagens de Componentes Principais (CPs), sendo que as cinco primeiras foram utilizadas para a análise. Desta forma, com a combinação de bandas, identificaram-se novas interfaces e feições, a partir da contribuição e representatividade de cada CP, que se configurou em cinco agrupamentos, denominados de Fisionomias: 1 (Norte- Planalto Meridional), 2 (Serra Geral), 3 (Depressão Central), 4 (Depósitos Aluviais), associadas aos mapas Hipsométrico/declividades com as CPs geradas e com os elementos da paisagem. Estas fisionomias expressaram as diferenças e/ou similaridades no uso da terra, permitindo o seu agrupamento, a partir das características do relevo, litologia, solos, vegetação e uso e cobertura da terra, destacando-se a considerável interferência antrópica na modificação da fisionomia da paisagem. / The integrated study of the landscape allows the verification of the interconnection levels, structure and functionality of various portions of the earth\'s surface. In this aspect, many researches have included as a theme, the study of the mechanisms of landscape functioning and the interaction between its components. In this way, it becomes essential for the expansion of the investigations, the introduction of methodologies and new techniques, that inserted properly, contribute to the better understanding of the elements that compose the landscape. Thus, this study aimed to identify, interpret and understand the diversity of physiognomy of the landscape and its physiology, in the hydrographic basin of river Botucaraí, Rio Grande do Sul, from the application of remote sensing techniques, specifically the Principal Component Analysis (PCA). In this perspective, it is understood that the treatment of the spectral bands, from satellite images, constitutes a complementation in the study and understanding of the constituent elements of the landscape: soil, relief, lithology and vegetation, besides generating cartographic products with more precise levels of detail. The PCA technique was applied from land use and land cover mapping, relief mapping, basic theme maps (hypsometry and declivity), the geological map, the vegetation cover map, and the soil map. Thus, the images of Principal Components (CPs) were generated, and the first five were used for the analysis. In this way, with the combination of bands, new interfaces and features were identified, based on the contribution and representativeness of each CP, which was configured in five groups, called Physiognomies: 1 (north- Planalto Meridional), 2 (Serra Geral), 3 (Central Depression), 4 (Alluvial deposits) associated with Hypsometric maps/declivity with CPs generated and landscape elements. These physiognomies expressed the differences and/or similarities in the land use, allowing their grouping, from the characteristics of the relief, lithology, soils, vegetation and use and cover of the land, highlighting the considerable anthropic interference in the modification of the physiognomy of the landscape.

Dans une situation de forte vulnérabilité induite par les crises laitières de 2009 et 2014-2016, de nombreux éleveurs laitiers se convertissent à l’AB qui semble une alternative prometteuse. Mais la conversion à l’AB est une période de changements de pratiques agricoles, d'interlocuteurs de conseil, etc. sources d’incertitudes sans valorisation immédiate du lait au prix du lait AB avant 1 an ½ à 2 ans. Ce choix de conversion pose la question de la vulnérabilité des exploitations laitières, c’est à dire de leur capacité à faire face, à s’adapter ou à se remettre des effets de divers aléas avant, pendant et à l’issue de la conversion à l’AB. Ma thèse visait à évaluer si la conversion à l’AB est un moyen de réduire la vulnérabilité des exploitations laitières. Pour ce faire, je me suis appuyée sur trois dispositifs de suivis d’éleveurs laitiers à différents moments de leur conversion à l’AB. Au plan de la production de connaissances, ce travail montre que la conversion à l’AB peut être un levier important pour la réduction de la vulnérabilité des exploitations agricoles à condition de s’orienter vers un système à dominante herbagère. Au plan méthodologique, la principale originalité de mon travail réside dans le développement d’une méthode d’évaluation intégrée et dynamique de la vulnérabilité. / In a situation of high vulnerability induced by the 2009 and 2014-2016 milk crises, many dairy farmers convert to organic farming, which seems a promising alternative. But the conversion to organic farming is a period of changes in farming practices, farm consultants, etc. sources of uncertainties without immediate valuation of the milk at the organic price before 1 ½ to 2 years. This conversion decision raises the question of the vulnerability of dairy farms, i.e. their ability to cope with, adapt to or recover from the effects of various hazards before, during and after the conversion. My PhD project aimed to assess whether the conversion to organic farming is a way to reduce the vulnerability of dairy farms. To that end, my work relied on three research set-ups based on surveys with dairy farmers at different stages of their conversion to organic farming. In terms of knowledge production, this work shows that conversion to organic farming can be an important lever to reduce farms vulnerability, as long as they move towards pasture-based system. In terms of methodological production, the main originality of my work lies in the development of an integrated and dynamic method for vulnerability assessment.