We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.genome architecture | molecular dynamics | CTCF | chromatin loops | CRISPR
We propose a novel automatic target recognition (ATR) system for classification of three types of ground vehicles in the moving and stationary target acquisition and recognition (MSTAR) public release database. First, MSTAR image chips are represented as fine and raw feature vectors, where raw features compensate for the target pose estimation error that corrupts fine image features. Then, the chips are classified by using the adaptive boosting (AdaBoost) algorithm with the radial basis function (RBF) network as the base learner. Since the RBF network is a binary classifier, we decompose our multiclass problem into a set of binary ones through the error-correcting output codes (ECOC) method, specifying a dictionary of code words for the set of three possible classes. AdaBoost combines the classification results of the RBF network for each binary problem into a code word, which is then "decoded" as one of the code words (i.e., ground-vehicle classes) in the specified dictionary. Along with classification, within the AdaBoost framework, we also conduct efficient fusion of the fine and raw image-feature vectors. The results of large-scale experiments demonstrate that our ATR scheme outperforms the state-of-the-art systems reported in the literature.
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