bioRxiv Science⌕ Search

Biology subjects

Yuille, A.

Publications and source records attributed to Yuille, A..

2 recordsLinked to original sources

Cue-Invariant Geometric Structure of the Population Codes in Macaque V1 and V2

AO_SCPLOWBSTRACTC_SCPLOWOur ability to recognize objects and scenes, whether they appear in photographs, cartoons, or simple line drawings, is striking. Studies have shown that infants, members of isolated Stone Age tribes, and non-human primates can readily identify objects from line drawings. These findings suggest that the brain may inherently generate neural representations that align across different rendering cues, enabling abstraction. To test this hypothesis, we investigated the representational invariance of complex patterns of surface boundaries found in natural scenes. We tested whether individual neurons in V1 and V2 of the macaque monkey responded similarly to the presentation of these patterns across different renderings (i.e., as contours, luminance-defined patches, and segments of natural images). We found that individual neurons exhibit some degree of tuning invariance, stronger in V1 than in V2. At the population level, as a means to assess cue-invariant abstract representation, we measured decoding accuracy across cues ( cue-transfer decoding). We found that this decoding is greatly enhanced when a geometric transformation (Procrustes Transformation) is first performed to align the population activities across cues. It is also effective when applied to different populations of neurons within or across visual areas. These results were compared with populations of artificial neurons from models of the ventral visual streams, further indicating that cue-invariance stabilizes with population size. In summary, we found that while individual neurons exhibit some cue-invariance properties, the stability of the population geometry emerges as a more robust candidate for supporting a cue-invariant representation of visual information in the early visual areas. SIGNIFICANT STATEMENTHow can we easily recognize objects and scenes in a wide range of renderings, such as photographs, cartoons, or line drawings? One possibility is that our visual system processes information using an invariant representation. To investigate this hypothesis, we designed a stimulus set made of boundary patterns extracted from natural scenes, and displayed using three distinct renderings. We found that, while the tuning preference of individual V1 and V2 neurons displayed some correlation across renderings, a more robust invariant representation could be achieved when analyzing neural population geometry. Overall, we found that a cue-invariant representation of visual elements in the early visual areas may rest primarily on the geometry of the population responses, rather than individual neurons tuning characteristics.

neuroscience↗

Three-dimensional genomic mapping of human pancreatic tissue reveals striking multifocality and genetic heterogeneity in precancerous lesions

Pancreatic intraepithelial neoplasia (PanIN) is a precursor to pancreatic cancer and represents a critical opportunity for cancer interception. However, the number, size, shape, and connectivity of PanINs in human pancreatic tissue samples are largely unknown. In this study, we quantitatively assessed human PanINs using CODA, a novel machine-learning pipeline for 3D image analysis that generates quantifiable models of large pieces of human pancreas with single-cell resolution. Using a cohort of 38 large slabs of grossly normal human pancreas from surgical resection specimens, we identified striking multifocality of PanINs, with a mean burden of 13 spatially separate PanINs per cm3 of sampled tissue. Extrapolating this burden to the entire pancreas suggested a median of approximately 1000 PanINs in an entire pancreas. In order to better understand the clonal relationships within and between PanINs, we developed a pipeline for CODA-guided multi-region genomic analysis of PanINs, including targeted and whole exome sequencing. Multi-region assessment of 37 PanINs from eight additional human pancreatic tissue slabs revealed that almost all PanINs contained hotspot mutations in the oncogene KRAS, but no gene other than KRAS was altered in more than 20% of the analyzed PanINs. PanINs contained a mean of 13 somatic mutations per region when analyzed by whole exome sequencing. The majority of analyzed PanINs originated from independent clonal events, with distinct somatic mutation profiles between PanINs in the same tissue slab. A subset of the analyzed PanINs contained multiple KRAS mutations, suggesting a polyclonal origin even in PanINs that are contiguous by rigorous 3D assessment. This study leverages a novel 3D genomic mapping approach to describe, for the first time, the spatial and genetic multifocality of human PanINs, providing important insights into the initiation and progression of pancreatic neoplasia.

cancer biology↗