arXiv subjects

Abicumaran Uthamacumaran

Publications and source records attributed to Abicumaran Uthamacumaran.

24 records · Page 2Linked to original sources

arXiv2024

On the Salient Limitations of the Methods of Assembly Theory and their Classification of Molecular Biosignatures

We demonstrate that the assembly pathway method underlying assembly theory (AT) is an encoding scheme widely used by popular statistical compression algorithms. We show that in all cases (synthetic or natural) AT performs similarly to other simple coding schemes and underperforms compared to system-related indexes based upon algorithmic probability that take into account statistical repetitions but also the likelihood of other computable patterns. Our results imply that the assembly index does not offer substantial improvements over existing methods, including traditional statistical ones, and imply that the separation between living and non-living compounds following these methods has been reported before.

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arXiv2022

A Review of Mathematical and Computational Methods in Cancer Dynamics

Cancers are complex adaptive diseases regulated by the nonlinear feedback systems between genetic instabilities, environmental signals, cellular protein flows, and gene regulatory networks. Understanding the cybernetics of cancer requires the integration of information dynamics across multidimensional spatiotemporal scales, including genetic, transcriptional, metabolic, proteomic, epigenetic, and multi-cellular networks. However, the time-series analysis of these complex networks remains vastly absent in cancer research. With longitudinal screening and time-series analysis of cellular dynamics, universally observed causal patterns pertaining to dynamical systems, may self-organize in the signaling or gene expression state-space of cancer triggering processes. A class of these patterns, strange attractors, may be mathematical biomarkers of cancer progression. The emergence of intracellular chaos and chaotic cell population dynamics remains a new paradigm in systems oncology. As such, chaotic and complex dynamics are discussed as mathematical hallmarks of cancer cell fate dynamics herein. Given the assumption that time-resolved single-cell datasets are made available, a survey of interdisciplinary tools and algorithms from complexity theory, are hereby reviewed to investigate critical phenomena and chaotic dynamics in cancer ecosystems. To conclude, the perspective cultivates an intuition for computational systems oncology in terms of nonlinear dynamics, information theory, inverse problems and complexity. We highlight the limitations we see in the area of statistical machine learning but the opportunity at combining it with the symbolic computational power offered by the mathematical tools explored.

q-bio.OT↗

arXiv2022

Machine Learning Characterization of Cancer Patients-Derived Extracellular Vesicles using Vibrational Spectroscopies

The early detection of cancer is a challenging problem in medicine. The blood sera of cancer patients are enriched with heterogeneous secretory lipid bound extracellular vesicles (EVs), which present a complex repertoire of information and biomarkers, representing their cell of origin, that are being currently studied in the field of liquid biopsy and cancer screening. Vibrational spectroscopies provide non-invasive approaches for the assessment of structural and biophysical properties in complex biological samples. In this pilot study, multiple Raman spectroscopy measurements were performed on the EVs extracted from the blood sera of 9 patients consisting of four different cancer subtypes (colorectal cancer, hepatocellular carcinoma, breast cancer and pancreatic cancer) and five healthy patients (controls). FTIR (Fourier Transform Infrared) spectroscopy measurements were performed as a complementary approach to Raman analysis, on two of the four cancer subtypes. The AdaBoost Random Forest Classifier, Decision Trees, and Support Vector Machines (SVM) distinguished the baseline corrected Raman spectra of cancer EVs from those of healthy controls (18 spectra) with a classification accuracy of above 90 percent when reduced to a spectral frequency range of 1800 to 1940 inverse cm and subjected to a 50:50 training: testing split. FTIR classification accuracy on 14 spectra showed an 80 percent classification accuracy. Our findings demonstrate that basic machine learning algorithms are powerful applied intelligence tools to distinguish the complex vibrational spectra of cancer patient EVs from those of healthy patients. These experimental methods hold promise as valid and efficient liquid biopsy for artificial intelligence-assisted early cancer screening.

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arXiv2022

Machine Intelligence-Driven Classification of Cancer Patients-Derived Extracellular Vesicles using Fluorescence Correlation Spectroscopy: Results from a Pilot Study

Patient-derived extracellular vesicles (EVs) that contains a complex biological cargo is a valuable source of liquid biopsy diagnostics to aid in early detection, cancer screening, and precision nanotherapeutics. In this study, we predicted that coupling cancer patient blood-derived EVs to time-resolved spectroscopy and artificial intelligence (AI) could provide a robust cancer screening and follow-up tools. Methods: Fluorescence correlation spectroscopy (FCS) measurements were performed on 24 blood samples-derived EVs. Blood samples were obtained from 15 cancer patients (presenting 5 different types of cancers), and 9 healthy controls (including patients with benign lesions). The obtained FCS autocorrelation spectra were processed into power spectra using the Fast-Fourier Transform algorithm and subjected to various machine learning algorithms to distinguish cancer spectra from healthy control spectra. Results and Applications: The performance of AdaBoost Random Forest (RF) classifier, support vector machine, and multilayer perceptron, were tested on selected frequencies in the N=118 power spectra. The RF classifier exhibited a 90% classification accuracy and high sensitivity and specificity in distinguishing the FCS power spectra of cancer patients from those of healthy controls. Further, an image convolutional neural network (CNN), ResNet network, and a quantum CNN were assessed on the power spectral images as additional validation tools. All image-based CNNs exhibited a nearly equal classification performance with an accuracy of roughly 82% and reasonably high sensitivity and specificity scores. Our pilot study demonstrates that AI-algorithms coupled to time-resolved FCS power spectra can accurately and differentially classify the complex patient-derived EVs from different cancer samples of distinct tissue subtypes.

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arXiv2021

Pattern Detection on Glioblastoma's Waddington landscape via Generative Adversarial Networks

Glioblastoma (GBM) is a highly morbid and lethal disease with poor prognosis. Their emergent properties such as cellular heterogeneity, therapy resistance, and self-renewal are largely attributed to the interactions between a subset of their population known as glioblastoma-derived stem cells (GSCs) and their microenvironment. Identifying causal patterns in the developmental trajectories between GSCs and the mature, well-differentiated GBM phenotypes remains a challenging problem in oncology. The paper presents a blueprint of complex systems approaches to infer attractor dynamics from the single-cell gene expression datasets of pediatric GBM and adult GSCs. These algorithms include Waddington landscape reconstruction, Generative Adversarial Networks, and fractal dimension analysis. Here I show, a Rossler-like strange attractor with a fractal dimension of roughly 1.7 emerged in the GAN-reconstructed patterns of all twelve patients. The findings suggest a strange attractor may be driving the complex dynamics and adaptive behaviors of GBM in signaling state-space.

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arXiv2021

A Review of Complex Systems Approaches to Cancer Networks

Cancers remain the lead cause of disease-related, pediatric death in North America. The emerging field of complex systems has redefined cancer networks as a computational system with intractable algorithmic complexity. Herein, a tumor and its heterogeneous phenotypes are discussed as dynamical systems having multiple, strange attractors. Machine learning, network science and algorithmic information dynamics are discussed as current tools for cancer network reconstruction. Deep Learning architectures and computational fluid models are proposed for better forecasting gene expression patterns in cancer ecosystems. Cancer cell decision-making is investigated within the framework of complex systems and complexity theory.

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