Biology subjects

Brock, O.

Publications and source records attributed to Brock, O..

5 recordsLinked to original sources

bioRxiv2024

An Information Processing Pattern from Robotics Predicts Properties of the Human Visual System

We tested the hypothesis that an algorithmic information processing pattern from robotics, Active InterCONnect (AICON), could serve as a useful representation for exploring human vision. We created AICON-based computational models for two visual illusions: the shape-contingent color aftereffect and silencing by motion. The models reproduced the effects seen in humans and generated surprising and novel predictions that we validated through human psychophysical experiments. Inconsistencies between model predictions and experimental results were resolved through iterative model adjustments. For the shape-contingent color aftereffect, the model predicted and experiments confirmed weaker aftereffects for outline shape manipulations and individual differences in perceived aftereffects. For silencing by motion, the model predicted and experiments validated unexpected trends as well as individual differences. Our findings demonstrate AICONs ability to capture relevant aspects of human visual information processing including variability across individuals. It highlights the potential for novel collaborations between synthetic and biological disciplines.

neuroscience↗

bioRxiv2023

Modelling protein complexes with crosslinking mass spectrometry and deep learning

Scarcity of structural and evolutionary information on protein complexes poses a challenge to deep learning-based structure modelling. We integrated experimental distance restraints obtained by crosslinking mass spectrometry (MS) into AlphaFold-Multimer, by extending AlphaLink to protein complexes. Integrating crosslinking MS data substantially improves modelling performance on challenging targets, by helping to identify interfaces, focusing sampling, and improving model selection. This extends to single crosslinks from whole-cell crosslinking MS, opening the possibility of whole-cell structural investigations driven by experimental data. We demonstrate this by revealing the molecular basis of iron homeostasis in Bacillus subtilis.

bioinformatics↗

bioRxiv2022

DomainRank: Improving Biological Data Sets With Domain Knowledge and Google's PageRank

MotivationThe quality of biological data crucially affects progress in science. This quality can be improved with better measurement devices, more sophisticated experimental designs, or repetitious measurements. Each of these options is associated with substantial costs. We present a simple computational tool as an alternative. This algorithmic tool, called DomainRank, leverages simple domain knowledge and overlapping information content in biological network data to improve measurement quality at a negligible cost. Following the simple computational template of Domain-Rank, researchers can boost the confidence of their own data with little effort. ResultsWe demonstrate the performance of DomainRank in three test cases: DomainRank finds 14.9% more interactions in quantitative proteomics experiments, improves the precision of predicted residue-residue contacts from co-evolutionary data by up to 11.6% (averaged over 882 proteins), and identifies 89.2% more cross-links in photo-crosslinking/mass spectrometry (photo-CLMS) experiments. Although our proposed template is specialized on biological network data, we view this approach as an universal computational tool for data improvement that could be routinely applied in many disciplines. AvailabilityAn implementation of DomainRank is freely available: https://github.com/Rappsilber-Laboratory/pagerank-refine

bioinformatics↗

bioRxiv2022

A role for thalamic projection GABAergic neurons in circadian responses to light

The thalamus is an important hub for sensory information and participates in sensory perception, regulation of attention, arousal and sleep. These functions are executed primarily by glutamatergic thalamocortical neurons that extend axons to the cortex and initiate cortico-thalamocortical connectional loops. However, the thalamus also contains projection GABAergic neurons that do not engage in direct communication with the cortex. Here, we have harnessed recent insight into the development of the intergeniculate (IGL), the ventrolateral geniculate (LGv) and the perihabenula (pHB) to specifically target and manipulate thalamic projection GABAergic neurons in female and male mice. Our results show that thalamic GABAergic neurons of the IGL and LGv receive retinal input from diverse classes of ipRGCs, but not from the M1 ipRGC type, while those in the pHB lack direct retinal input. We describe the synergistic role of the photoreceptor melanopsin and the thalamic neurons of the IGL/LGv in circadian entrainment to dim light. We identify a requirement for the thalamic IGL/LGv in the rapid changes in vigilance states associated with circadian light transitions. Furthermore, we map a previously undescribed thalamic network of developmentally related GABAergic neurons in the IGL/LGv complex and the pHB potentially involved in light-dependent mood regulation. Significance statementThe intergeniculate leaflet and ventral geniculate nucleus are part of the extended circadian system and mediate some non-image-forming visual functions. Here we show that each of these structures has a thalamic (dorsal) as well as prethalamic (ventral) developmental origin. We map the retinal input to thalamus-derived cells in the IGL/LGv complex and discover that while ipRGC input is dominant, this is not likely to originate from M1-ipRGCs. We describe the extent of similarity in synaptic input to developmentally related cells in the IGL/LGv and in the perihabenula nucleus (pHB). We implicate thalamic cells in the IGL/LGv in vigilance state transitions at circadian light changes and in overt behavioural entrainment to dim light, the latter exacerbated by concomitant loss of melanopsin expression.

neuroscience↗

bioRxiv2017

Distinctive Behavioural Anomalies, Structural Brain Phenotypes And Cortical Hyper-Connectivity In Chd8-Deficient Mice

Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. To investigate how reduced Chd8 gene dosage may disrupt brain development and predispose individuals to ASD, we generated a Chd8 heterozygous mouse model. In line with clinical observations, we found that Chd8 heterozygous mice displayed subtle brain hyperplasia and hypertelorism, coupled with increased postnatal brain weight. Chd8 heterozygous mice displayed anomalous behaviours, but autism-like social deficits, repetitive and restricted behaviours were not present. Only minor gene expression changes were observed in the embryonic neocortex at E12.5, with more pronounced gene expression changes in postnatal cortex at P5. Differentially expressed genes showed highly significant enrichment for known autism candidates. Amongst the down-regulated transcripts, genes involved in cell adhesion and axon guidance were particularly prominent, implicating impaired connectivity as a potential mechanism underlying the ASD phenotype. To probe this further, we performed resting state functional fMRI and found increased synchronised activity in cortico-hippocampal and auditory-parietal networks, hinting at impaired sensory processing. Together, these data show that Chd8 heterozygous mice recapitulate key clinical features found in patients with CHD8 mutations and show a unique combination of behavioural phenotypes, which may be underpinned by a distinctive disruption of brain connectivity and sensory processing.

neuroscience↗