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Murta, T.

Publications and source records attributed to Murta, T..

3 recordsLinked to original sources

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

With colorectal cancer (CRC) being the second most common cause of cancer-related deaths worldwide1, there is an urgent need for better diagnostic tools and new, more targeted therapies. Here we used genetically engineered mouse models (GEMMs), and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that unsupervised metabolic profiling can stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging (MSI) to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-mutant CRC, and propose one of its enzymes, i.e. adenosylhomocysteinase (AHCY), as a new therapeutic target. Collectively, we show that the profound genotype-dependent alterations in both lipid and small molecule metabolism in CRC may be exploited for tissue classification with no need for ion identification, and we applied further data analysis to expose a novel metabolic vulnerability of CRC.

cancer biology↗

Training a neural network to learn other dimensionality reduction removes data size restrictions in bioinformatics and provides a new route to exploring data representations

High dimensionality omics and hyperspectral imaging datasets present difficult challenges for feature extraction and data mining due to huge numbers of features that cannot be simultaneously examined. The sample numbers and variables of these methods are constantly growing as new technologies are developed, and computational analysis needs to evolve to keep up with growing demand. Current state of the art algorithms can handle some routine datasets but struggle when datasets grow above a certain size. We present a training deep learning via neural networks on non-linear dimensionality reduction, in particular t-distributed stochastic neighbour embedding (t-SNE), to overcome prior limitations of these methods. One Sentence SummaryAnalysis of prohibitively large datasets by combining deep learning via neural networks with non-linear dimensionality reduction.

bioinformatics↗

Measurement of the mapping between intracranial EEG and fMRI recordings in the human brain

There are considerable gaps in our understanding of the relationship between human brain activity measured at different temporal and spatial scales by intracranial electroencephalography and fMRI. By comparing individual features and summary descriptions of intracranial EEG activity we determined which best predict fMRI changes in the sensorimotor cortex in two brain states: at rest and during motor performance. We also then examine the specificity of this relationship to spatial colocalisation of the two signals.\n\nWe acquired electrocorticography and fMRI simultaneously (ECoG-fMRI) in the sensorimotor cortex of 3 patients with epilepsy. During motor activity, high gamma power was the only frequency band where the electrophysiological response was colocalised with fMRI measures across all subjects. The best model of fMRI changes was its principal components, a parsimonious description of the entire ECoG spectrogram. This model performed much better than a model based on the classical frequency bands both during task and rest periods or models derived on a summary of cross spectral changes (e.g. root mean squared EEG frequency). This suggests that the region specific fMRI signal is reflected in spatially and spectrally distributed EEG activity.

neuroscience↗