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Biology subjects

Chulian, S.

Publications and source records attributed to Chulian, S..

2 recordsLinked to original sources

Automatic computational classification of bone marrow cells for B cell pediatric leukemia using UMAP

B Acute Lymphoblastic Leukemia (B-ALL) accounts for approximately 80% of pediatric leukemia cases. Despite treatment advances, 15-20% of children experience relapse, highlighting the need of improved monitoring of patients and novel strategies leading to successful therapies. Flow Cytometry is an essential technique for measuring residual disease and guiding treatment. However, traditional manual gating limits its efficiency. In recent years, computational tools have been integrated to enhance these clinical processes but many mathematical techniques are underexploited. Particularly, Uniform Manifold Approximation and Projection (UMAP), together with Machine Learning, provide promising approaches for analyzing large datasets. Mathematical tools and artificial intelligence offer new perspectives on these health problems, beyond the usual approach in biomedicine. We have exploited 234 samples from 75 B-ALL patients to develop an artificial intelligence-based algorithm that can improve patient classification and therapy decisions in different patient cohorts. This implies an advancement on the routine manual analysis of the disease progression, as we identify key subpopulations automatically, distinguishing patients bone marrow regeneration patterns, thus improving the prediction and prognosis of the disease. MSC Classification: 68-04, 68T09, 90C90, 92B05 Abbreviations: A list of abbreviations used throughout this work can be found in Appendix A.

cancer biology↗

Breaking Down Cell-Free DNA Fragmentation: A Markov Model Approach

Cell-free DNA (cfDNA) is released into the bloodstream from cells in various physiological and pathological conditions. The use of cfDNA as a non-invasive biomarker has attracted attention, but the dynamics of cfDNA fragmentation in the bloodstream are not well understood and have not been previously studied computationally. To address this issue, we present a Markovian model called FRIME (Fragmentation, Immigration, and Exit) that captures three leading mechanisms governing cfDNA fragmentation in the bloodstream. The FRIME model enables the simulation of cfDNA fragment profiles by sampling from the stationary distribution of FRIME processes. By varying the parameters of our model, we generate fragment profiles similar to those observed in liquid biopsies and provide insight into the underlying biological mechanisms driving the fragmentation dynamics. To validate our model, we compare simulated FRIME profiles with mitochondrial and genomic cfDNA fragment profiles. Our simulation results are consistent with experimental and clinical observations and highlight potential physicochemical differences between mitochondrial and genomic cfDNA. The FRIME simulation framework provides an initial step towards an improved computational understanding of DNA fragmentation dynamics in the bloodstream and may aid in the analysis of liquid biopsy data. Author summaryCell-free DNA (cfDNA) released into the bloodstream from cells in different conditions is the basis for liquid biopsies, thus being non-invasive biomarkers of potential interest. However, the dynamics of cfDNA fragmentation in the bloodstream remain poorly understood and are yet to be studied computationally. To address this issue, we developed a Markovian model which captures the three leading mechanisms governing cfDNA fragmentation in the bloodstream: FRagmentation, IMmigration, and Exit (FRIME). The FRIME model enables the simulation of cfDNA fragment profiles by sampling from the stationary distribution of FRIME processes. Simulation results are compared with mitochondrial and genomic cfDNA fragment profiles, which show consistency with experimental and clinical observations. The FRIME simulation framework is a significant step towards understanding DNA fragmentation dynamics in the bloodstream, uncovering potential physicochemical differences between mitochondrial and genomic cfDNA, and aiding the analysis of liquid biopsy data.

bioinformatics↗