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Documents  92-08 | enregistrements trouvés : 4

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Differences in disease predisposition or response to treatment can be explained in great part by genomic differences between individuals. This has given birth to precision medicine, where treatment is tailored to the genome of patients. This field depends on collecting considerable amounts of molecular data for large numbers of individuals, which is being enabled by thriving developments in genome sequencing and other high-throughput experimental technologies.
Unfortunately, we still lack effective methods to reliably detect, from this data, which of the genomic features determine a phenotype such as disease predisposition or response to treatment. One of the major issues is that the number of features that can be measured is large (easily reaching tens of millions) with respect to the number of samples for which they can be collected (more usually of the order of hundreds or thousands), posing both computational and statistical difficulties.
In my talk I will discuss how to use biological networks, which allow us to understand mutations in their genomic context, to address these issues. All the methods I will present share the common hypotheses that genomic regions that are involved in a given phenotype are more likely to be connected on a given biological network than not.
Differences in disease predisposition or response to treatment can be explained in great part by genomic differences between individuals. This has given birth to precision medicine, where treatment is tailored to the genome of patients. This field depends on collecting considerable amounts of molecular data for large numbers of individuals, which is being enabled by thriving developments in genome sequencing and other high-throughput ex...

92C42 ; 92-08 ; 92B15 ; 62P10

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Breast cancer is the most common type of cancer among women and despite recent advances in the medical field, there are still some inherent limitations in the currently used screening techniques. The radiological interpretation of X-ray mammograms often leads to over-diagnosis and, as a consequence, to unnecessary traumatic and painful biopsies. First we use the 1D Wavelet Transform Modulus Maxima (WTMM) method to reveal changes in skin temperature dynamics of women breasts with and without malignant tumor. We show that the statistics of temperature temporal fluctuations about the cardiogenic and vasomotor perfusion oscillations do not change across time-scales for cancerous breasts as the signature of homogeneous monofractal fluctuations. This contrasts with the continuous change of temperature fluctuation statistics observed for healthy breasts as the hallmark of complex multifractal scaling. When using the 2D WTMM method to analyze the roughness fluctuations of X-ray mammograms, we reveal some drastic loss of roughness spatial correlations that likely results from some deep architectural change in the microenvironment of a breast tumor. This local breast disorganisation may deeply affect heat transfer and related thermomechanics in the breast tissue and in turn explain the loss of multifractal complexity of temperature temporal fluctuations previously observed in mammary glands with malignant tumor. These promising findings could lead to the future use of combined wavelet-based multifractal processing of dynamic IR thermograms and X-ray mammograms to help identifying women with high risk of breast cancer prior to more traumatic examinations. Besides potential clinical impact, these results shed a new light on physiological changes that may precede anatomical alterations in breast cancer development.

Keywords: breast cancer - X-ray mammography - infrared thermography - multifractal analysis - wavelet transform - wavelet transform modulus maxima method
Breast cancer is the most common type of cancer among women and despite recent advances in the medical field, there are still some inherent limitations in the currently used screening techniques. The radiological interpretation of X-ray mammograms often leads to over-diagnosis and, as a consequence, to unnecessary traumatic and painful biopsies. First we use the 1D Wavelet Transform Modulus Maxima (WTMM) method to reveal changes in skin ...

92-08 ; 92C50 ; 92C55

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In the second talk, I will present some of our work on this area. Our work on this area, where we have focused on transcriptomics and (phospho)proteomics to study signaling networks. Our tools range from a meta-resource of biological knowledge (Omnipath) to methods to infer pathway and transcription factor activities (PROGENy and DoRothEA, respectively) from gene expression and subsequently infer causal paths among them (CARNIVAL), to tools to infer logic models from phosphoproteomic and phenotypic data (CellNOpt and PHONEMeS). We have recently adapted these tools to single-cell data. I will illustrate their utility in cases of biomedical relevance, in particular to improve our understanding of cancer and to develop novel therapeutic opportunities. As main application I will discuss our work analysing, as a model for personalized medicine, large pharmaco-genomic screenings in cell lines. These screenings provide rich information about alterations in tumours that confer drug sensitivity or resistance. Integration of this data with prior knowledge provides biomarkers and offer hypotheses for novel combination therapies. Our own analysis as well as the results of a crowdsourcing effort (as part of a DREAM
challenge) reveals that prediction of drug efficacy from basal omics data is that discussed above is far from accurate, implying important limitations for personalised medicine. An important aspect that deserves detailed attention is the dynamics of signaling networks and how they response to perturbations such as drug treatment.
I will present how cell-specific logic models, trained with measurements upon perturbations, can provides new biomarkers and treatment opportunities not noticeable by static molecular characterisation.
In the second talk, I will present some of our work on this area. Our work on this area, where we have focused on transcriptomics and (phospho)proteomics to study signaling networks. Our tools range from a meta-resource of biological knowledge (Omnipath) to methods to infer pathway and transcription factor activities (PROGENy and DoRothEA, respectively) from gene expression and subsequently infer causal paths among them (CARNIVAL), to tools to ...

92B05 ; 92-08 ; 92-10 ; 92C42

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Modern technologies allow us to profile in high detail biomedical samples at fast decreasing costs. New technologies are opening new data modalities, in particular to measure at the single cell level. Prior knowledge, and biological networks in particular, are useful to integrate this data and distill mechanistic insight. This can help to interpret the result of machine learning or statistical analysis, as well as generate input features for these methods. In addition, they can be converted in dynamic mechanistic models to gain more specific insight. I will give an overview of these approaches showcasing some examples and approaches used in the field.
Modern technologies allow us to profile in high detail biomedical samples at fast decreasing costs. New technologies are opening new data modalities, in particular to measure at the single cell level. Prior knowledge, and biological networks in particular, are useful to integrate this data and distill mechanistic insight. This can help to interpret the result of machine learning or statistical analysis, as well as generate input features for ...

92B05 ; 92-08 ; 92-10 ; 92C42

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