Werner, J. | Search bioRxiv

bioRxiv2017

Framework For Quality Assessment Of Whole Genome, Cancer Sequences

Working with cancer whole genomes sequenced over a period of many years in different sequencing centres requires a validated framework to compare the quality of these sequences. The Pan-Cancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Consortium (ICGC), a project a cohort of over 2800 donors provided us with the challenge of assessing the quality of the genome sequences. A non-redundant set of five quality control (QC) measurements were assembled and used to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses of these whole genome sequences. The resulting QC measures also allowed for exclusion samples of poor quality, providing researchers within PCAWG, and when the data is released for other researchers, a good idea of the sequencing quality. For a researcher wishing to apply the QC measures for their data we provide a Docker Container of the software used to calculate them. We believe that this is an effective framework of quality measures for whole genome, cancer sequences, which will be a useful addition to analytical pipelines, as it has to the PCAWG project.

genomics↗

bioRxiv2017

Non-monotonic spatial structure of interneuronal correlations in prefrontal microcircuits

Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in non-monotonic correlation structures. Here we show such a spatially non-monotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A non-monotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.\n\nSignificance statementThe spatial structure of correlated activity of neurons in lower-order visual areas has been shown to linearly decrease as a measure of distance. The shape of correlated variability is a defining feature of cortical microcircuits as it constrains the computational power and diversity of a region. We show here for the first time a non-monotonic spatial structure of functional connectivity in the pre-frontal cortex where distal interactions are just as strong as proximal interactions during visual engagement of functionally similar PFC neurons. Such a nonmonotonic structure of functional connectivity could have far-reaching consequences in rethinking the nature and the role of prefrontal microcircuits in various cognitive states.

neuroscience↗