Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels

Abstract Next generation sequencing of cell-free DNA (cfDNA) is a promising method for treatment monitoring and therapy selection in metastatic breast cancer (MBC). However, distinguishing tumor-specific variants from sequencing artefacts and germline variation with low false discovery rate is challenging when using large targeted sequencing panels covering many tumor suppressor genes. To address this, we built a machine learning model to remove false positive variant calls and augmented it with additional filters to ensure selection of tumor-derived variants. We used cfDNA of 70 MBC patients profiled with both the small targeted Oncomine breast panel (Thermofisher) and the much larger Qiaseq Human Breast Cancer Panel (Qiagen). The model was trained on the panels’ common regions using Oncomine hotspot mutations as ground truth. Applied to Qiaseq data, it achieved 35% sensitivity and 36% precision, outperforming basic filtering. For 20 patients we used germline DNA to filter for somatic variants and obtained 245 variants in total, while our model found seven variants, of which six were also detected using the germline strategy. In ten tumor-free individuals, our method detected in total one (potentially germline) variant, in contrast to 521 variants detected without our model. These results indicate that our model largely detects somatic variants

Effects of selective attention on perceptual filling-in

After few seconds, a figure steadily presented in peripheral vision becomes perceptually filled-in by its background, as if it "disappeared". We report that directing attention to the color, shape, or location of a figure increased the probability of perceiving filling-in compared to unattended figures, without modifying the time required for filling-in. This effect could be augmented by boosting attention. Furthermore, the frequency distribution of filling-in response times for attended figures could be predicted by multiplying the frequencies of response times for unattended figures with a constant. We propose that, after failure of figure-ground segregation, the neural interpolation processes that produce perceptual filling-in are enhanced in attended figure regions. As filling-in processes are involved in surface perception, the present study demonstrates that even very early visual processes are subject to modulation by cognitive factors

Impairments in spatial generalization of visual skills after V4 and TEO lesions in macaques

The authors tested the spatial generalization of shape and color discriminations in 2 monkeys, in which 3 visual field quadrants were affected, respectively, by lesions in area V4, TEO, or both areas combined. The fourth quadrant served as a normal control. The monkeys were trained to discriminate stimuli presented in a standard location in each quadrant, followed by tests of discrimination performance in new locations in the same quadrant. In the quadrant affected by the V4 + TEO lesion, the authors found temporary but striking deficits in spatial generalization of shape and color discriminations over small distances, suggesting a contribution of areas V4 and TEO to short-range spatial generalization of visual skills