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Biology subjects

Minas, G.

Publications and source records attributed to Minas, G..

3 recordsLinked to original sources

Measuring developmental information encoded by a dynamicallandscape

During embryogenesis, as cells proliferate and assemble into tissues, they undergo a sequence of transitions between distinct molecular states eventually giving rise to a cellular population consisting of an appropriate distribution of specific functional cell types. Recent progress on the dynamics underlying decision-making in developmental landscape makes it feasible to start analysing the amount of information involved in constructing such systems. To explore this we introduce the notion of potency of a developmental landscape and attempt to calculate it for two development systems of current interest, in-vitro differentiation of epiblast-like cells into neural and mesodermal progenitors and the worm vulva patterning system. Our approach integrates concepts from developmental biology, information theory and dynamical systems to estimate both the number and identity of signalling regimes that give rise to distinguishable temporal response patterns.

developmental biology↗

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%. Current chemotherapeutic strategies only benefit a minority (20-30%) of patients and there are no methods available to differentiate between responders and non-responders. We performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1/2/3 vs TRG4/5) after chemotherapy, and differentially abundant proteins were compared. Protein depletion of highly abundant proteins led to the identification of around twice as many proteins. SWATH-MS revealed significant quantitative differences in the abundance of several proteins between the two groups. These included complement c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group. Of those that were found to be of higher abundance in the high TRG group, GSTP1 was found to exhibit the lowest p-value and highest classification accuracy and Cohens kappa value. Concentrations of these proteins were further examined using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers.

cancer biology↗

Multiplexing information flow through dynamic signalling systems

We consider how a signalling system can act as an information hub by multiplexing information arising from multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. While the results of this paper are theoretical, to motivate the idea of multiplexing, we provide experimental evidence that tentatively suggests that the NF-{kappa}B transcription factor can multiplex information about changes in multiple signals. We believe that our theoretical results may resolve the apparent paradox of how a system like NF-{kappa}B that regulates cell fate and inflammatory signalling in response to diverse stimuli can appear to have the low information carrying capacity suggested by recent studies on scalar signals. In carrying out our study, we introduce new methods for the analysis of large, nonlinear stochastic dynamic models, and develop computational algorithms that facilitate the calculation of fundamental constructs of information theory such as Kullback-Leibler divergences and sensitivity matrices, and link these methods to new theory about multiplexing information. We show that many current models such as those of the NF-{kappa}B system cannot multiplex effectively and provide models that overcome this limitation using post-transcriptional modifications.

systems biology↗