Biology subjects

Jeon, T.

Publications and source records attributed to Jeon, T..

5 recordsLinked to original sources

bioRxiv2024

A novel approach to digital characterisation of Tertiary Lymphoid Structures in colorectal cancer

Tertiary Lymphoid Structures (TLS) in cancer tissue are potential sites for the organisation of immune responses to cancer, and correlate positively with improved clinical outcomes for patients including in colorectal cancer (CRC). However it has proven challenging to standardise assessment of TLS due to the highly variable appearances of circumscribed domains of TLS within tissue sections. A recent three-dimensional reconstruction of TLS in CRC tissue showed that TLS are often large, multi-lobular structures, suggesting that assessing TLS across whole sections may be necessary to provide an accurate view of TLS activity in a patients tumour. In a pilot study we therefore used whole slide scans of multiplexed immunofluorescence images to characterise TLS from 22 subjects with CRC. Multiplexed staining for CD20, CD3, CD8, FoxP3 and Ki-67 enabled us to identify B-cells, CD8+ T cells, FoxP3- CD4 T-cells, and Foxp3+ CD4 T cells in all sections, and quantify both the presence of these cell subsets in lymphocytic clusters and their degree of proliferation within those clusters. In total we identified 524 lymphocytic clusters with morphology consistent with TLS. The count of TLS domains varied substantially between samples (from 4 to 100, mean 24) as did the proportion of total section area occupied by TLS (0.2%-7.8%) as well as size, morphology and cellular constituents; reflecting the intersection of the section plane with complex 3-dimensional structures. We quantified proliferation of B-cells and T-cell subsets within TLS domains across entire sections and compared to the canonical approach of counting and phenotyping individual TLS domains. The whole-slide approach proved far simpler than the canonical approach, generating digital summaries across our sample set clearly identifying patients with strikingly different levels of immune activity within their TLS. It also allowed us to demonstrate strong correlations between the proliferation of B-cells within CRC TLS and that of T-cell subsets. In summary we find that whole-section digital quantification of immune cell activity within TLS has major advantages over canonical approaches. Such whole-section approaches should accelerate research into correlations between TLS status and clinical outcomes, and ultimately enable standardised clinical tests based on automated analysis of multiplexed images.

cancer biology↗

bioRxiv2023

Development of Sensorimotor-Visual Connectome Gradient at Birth Predicts Cognitive Outcomes at 2 Years of Age

Functional connectome gradients represent fundamental brain organizing principles. Here, we investigate the maturation of the macroscopic connectome gradients in a task-free functional MRI dataset consisting of 39 preterm and term babies aged 31-42 postmenstrual weeks and its connection with postnatal cognitive growth. We show that the principal sensorimotor-to-visual gradient is present in baby connectomes around 35.6 postmenstrual weeks and continuously develops towards a more term-like pattern. The gradients global topographical structure undergoes progressive maturation with age, characterized by increases in explanation ratio, gradient range and gradient variation. The development of focal gradients is mostly localized in primary regions serving sensory, motor and visual functions. Machine learning approaches revealed that the connectome gradient at birth significantly predicts individual cognitive outcomes at 2-y follow-up. These findings highlight the early emerging rules of functional connectome gradients and have implications for understanding how the connectome gradients at birth underlies cognitive growth in later life. HighlightsO_LISensorimotor-to-visual gradient is present around 35.6 postmenstrual weeks C_LIO_LIGlobal gradient structure undergoes substantial changes during the third trimester C_LIO_LIRegional gradient develops mostly in primary sensory, motor, and visual regions C_LIO_LISensorimotor-to-visual gradient at birth predicts cognitive outcomes at age 2 C_LI

neuroscience↗

bioRxiv2023

Development of connectome dynamics at birth predicts neurocognitive outcomes at age 2

The functional connectome of the human brain comprises time-varying network structure that facilitates efficient inter-module communication and support flexible cognitive functions. However, little is known about how the connectome dynamics of the brain emerges and develops at very early stages of human life and whether this dynamics is predictive of neurocognitive outcomes later in life. Here, we employed resting-state functional MRI data from 39 infants (31 to 42 postmenstrual weeks) and a multilayer network model to characterize the development of connectome dynamics during the third trimester and its critical role in predicting future neurocognitive outcomes at 2 years of age. We observed that the modular architecture of baby functional connectomes spontaneously reconfigures over time, with lower network module switching across time primarily in the primary regions and higher module switching mainly in the association areas. With development, the dynamic switching between the brain modules was significantly decreased, primarily located in the lateral precentral gyrus, medial temporal lobe, and subcortical areas. The clustering analysis further revealed that the primary areas displayed a higher developmental rate than the higher-order systems. Using the support vector regression approach, we found that brain connectome dynamics at birth significantly predicted cognitive and language performance at 2 years of age. Our findings highlight the emergence and spatially inhomogeneous maturation of the neonate connectome dynamics, laying a critical neural foundation for the development of cognitive and language skills later in life.

neuroscience↗

bioRxiv2020

Diffusion-MRI-based regional cortical microstructure at birth for predicting neurodevelopmental outcomes at 2 years of age

Brain cerebral cortical architecture encoding regionally differential dendritic arborization and synaptic formation at birth underlies human behavior emergence at 2 years of age. Brain changes in 0-2 years are most dynamic across lifespan. Effective prediction of future behavior with brain microstructure at birth will reveal structural basis of behavioral emergence in typical development, and identify biomarkers for early detection and tailored intervention in atypical development. Here, we aimed to evaluate the neonate whole-brain cortical microstructure quantified by diffusion MRI for predicting future behavior. We found that individual cognitive and language functions assessed at age of 2 years were robustly predicted by neonate cortical microstructure using support vector regression. Remarkably, cortical regions contributing heavily to the prediction models exhibited distinctive functional selectivity for cognition and language. These findings highlight regional cortical microstructure at birth as potential sensitive biomarker in predicting future neurodevelopmental outcomes and identifying individual risks of brain disorders.

neuroscience↗

bioRxiv2017

Structural network maturation of the preterm human brain

During the 3rd trimester, large-scale of neural circuits are formed in the human brain, resulting in the adult-like brain networks at birth. However, how the brain circuits develop into a highly efficient and segregated connectome during this period is unknown. We hypothesized that faster increases of connectivity efficiency and strength at the brain hubs and rich-club are critical for emergence of an efficient and segregated brain connectome. Here, using high resolution diffusion MRI of 77 preterm-born and term-born neonates scanned at 31-42 postmenstrual weeks (PMW), we constructed the structural connectivity matrices and performed graph-theory-based analyses. We found faster increases of nodal efficiency mainly at the brain hubs, distributed in primary sensorimotor regions, superior-middle frontal and posterior cingulate gyrus during 31-42PMW. The rich-club and within-module connections were characterized by higher rates of edge strength increases. Edge strength of short-range connections increased faster than that of long-range connections. The nodal efficiencies of the hubs predicted individual postmenstrual ages more accurately than those of non-hubs. Collectively, these findings revealed regionally differentiated maturation in the baby brain structural connectome and more rapid increases of the hub and rich-club connections, which underlie network segregation and differentiated brain function emergence.

neuroscience↗