Siddiqui, M. | Search bioRxiv

bioRxiv2026

X-CODE: a dual RNA barcoding system for multi-platform clonal tracking and spatial phenotyping

Experimental dissection of clonal dynamics in complex tissues requires barcoding systems that are scalable, compatible with different analytical platforms, providing phenotypic and spatial resolution. Here we introduce X-CODE, a dual-expressed RNA barcoding system designed to enable high-complexity clonal tracking across sequencing-based, cytometric, and spatial imaging modalities within a unified experimental framework. X-CODE combines a combinatorial, probe-detectable long RNA barcode with a matched short sequencing barcode, enabling seamless integration of probe-based readouts with sequencing and barcode-guided clonal retrieval. We demonstrate robust X-CODE detection by mass cytometry and imaging-based platforms, including spatial RNA barcode readout using via a repurposed Akoya PhenoCycler-Fusion protocol. In addition, we show compatibility with MALDI mass spectrometry imaging for co-registration of clonal and metabolic information. We further demonstrate the feasibility of X-CODE detection within probe-based spatial transcriptomics using the 10x Genomics Xenium platform. Applied to an in vivo model of androgen deprivation in prostate cancer, X-CODE reveals clonal architecture, selection and clone-specific phenotypic and metabolic plasticity underlying castration resistance. Together, X-CODE provides a flexible and broadly accessible platform for integrated clonal analysis across spatial, phenotypic, and molecular dimensions.

cancer biology↗

bioRxiv2022

Mapping human social brain specialisation beyond the neuron using multimodal imaging in human infants

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of this process is based on evidence from unitary imaging modalities and has thus focused on isolated changes in spatial or temporal precision of neural or haemodynamic activation alone, giving an incomplete picture of the process. We speculate that neural specialisation of function will be underpinned by better coordinated haemodynamic and metabolic changes in a broader orchestrated physiological response. Thus, we present a harmonised framework in which specialisation is indexed by the emergence of coupling between neuronal activity and vascular supply of oxygen and energy. Here, we combine simultaneous measures of coordinated neural activity (EEG), metabolic rate and oxygenated blood supply (broadband near-infrared spectroscopy) to measure emerging specialisation in the infant brain. In 4-to-7-month-old infants, we show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high frequency brain activity. We conclude that functional specialisation of the brain is a coordinated activity across neural, haemodynamic, and metabolic changes, and our ability to measure these simultaneously opens new vistas in understanding how the brain is shaped by its environment.

developmental biology↗