Biology subjects

Whiting, F.

Publications and source records attributed to Whiting, F..

4 recordsLinked to original sources

bioRxiv2025

Patterns of brain-wide associations reflect socioeconomics

Previous brain-wide association studies (BWAS) cross-sectionally linked a specific behavioral trait, most commonly IQ or psychopathology, to variation in brain function or structure. Here, we expanded the focus of BWAS from effect sizes to interpretability and generalizability by mapping 649 variables to brain function and structure. We compared the resultant BWAS maps to other types of brain data to annotate the BWAS patterns. Socioeconomic status (SES) -- not IQ or psychopathology -- showed the strongest associations with both resting-state functional connectivity (RSFC) and cortical thickness in the Adolescent Brain Cognitive Development (ABCD) Study. A principal exposome brain pattern, anchored to sensory and motor cortex, captured 34% of the variance across all BWAS maps. This exposome pattern was strongly correlated with the SES and IQ BWAS maps and non-BWAS maps of sleep (EEG), norepinephrine (PET), and stimulants (drug trial), but not cognitive activation maps (task fMRI). Adjusting for SES, reduced brain-IQ associations by 40%. Brain with IQ associations did not generalize, as they could no longer be detected in subsamples drawn from only higher SES backgrounds, while brain with SES associations remained strong in higher-IQ-only subsamples. These findings reveal SES as the principal axis of population-level brain variation, possibly stemming from the sleep deprivation and heightened stress associated with lower SES, since socioeconomics can only indirectly affect the brain.

neuroscience↗

bioRxiv2025

Single cell multi-omic whole genome sequencing and chromatin accessibility profiling reveals genome-epigenome coevolution in colorectal cancer

Epigenetic alterations co-evolve with genetic mutations to drive carcinogenesis and treatment response. Resolving genome-epigenome coevolution requires accurate multi-omic single cell measurement. Here we develop a new technology called "double ATAC" (dATAC) for high-throughput, high-quality, concurrent whole genome sequencing and chromatin accessibility profiling of individual somatic cells. dATAC is a "one pot" method that uses two rounds of tagmentation to sequentially label open chromatin regions and then the whole genome, and produces data of the same quality as current leading single-omic methods. Using colorectal cancer as a model system, we apply dATAC to reveal convergent reorganisation of the epigenome across expanding drug-resistant clones during 5-FU chemotherapy exposure, remarkable stoichiometry of chromatin accessibility at somatic copy number alterations, and the clonal expansion of copy-number altered T cells in the stroma of metastatic disease. dATAC is a robust single cell technology to accurately profile genome-epigenome coevolution across tissues, diseases and species.

molecular biology↗

bioRxiv2024

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N [~] 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a motor structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

neuroscience↗

bioRxiv2019

Modeling adaptive therapy in non-muscle invasive bladder cancer

Bladder cancer is the 9th most commonly diagnosed cancer. Nearly half of patients with early stage bladder cancer treated with the immune-stimulating agent BCG have disease recurrence, while 13% progress to invasive bladder cancer. Here we explored the potential of tumor mutational heterogeneity and the role of pro- and anti-inflammatory cytokines to identify different subtypes of bladder cancer that may predict therapeutic response to BCG. Further, we used mathematical modeling of dosing strategies to infer tumor response to varying doses and time schedules f BCG administration. As a proof-of-concept, present adaptive therapy scheduling of BCG as a viable strategy to control tumor size and minimize recurrence.

cancer biology↗