Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration.

We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer

Adaptive Segmentation of Knee Radiographs for Selecting the Optimal ROI in Texture Analysis

The purposes of this study were to investigate: 1) the effect of placement of region-of-interest (ROI) for texture analysis of subchondral bone in knee radiographs, and 2) the ability of several texture descriptors to distinguish between the knees with and without radiographic osteoarthritis (OA). Bilateral posterior-anterior knee radiographs were analyzed from the baseline of OAI and MOST datasets. A fully automatic method to locate the most informative region from subchondral bone using adaptive segmentation was developed. We used an oversegmentation strategy for partitioning knee images into the compact regions that follow natural texture boundaries. LBP, Fractal Dimension (FD), Haralick features, Shannon entropy, and HOG methods were computed within the standard ROI and within the proposed adaptive ROIs. Subsequently, we built logistic regression models to identify and compare the performances of each texture descriptor and each ROI placement method using 5-fold cross validation setting. Importantly, we also investigated the generalizability of our approach by training the models on OAI and testing them on MOST dataset.We used area under the receiver operating characteristic (ROC) curve (AUC) and average precision (AP) obtained from the precision-recall (PR) curve to compare the results. We found that the adaptive ROI improves the classification performance (OA vs. non-OA) over the commonly used standard ROI (up to 9% percent increase in AUC). We also observed that, from all texture parameters, LBP yielded the best performance in all settings with the best AUC of 0.840 [0.825, 0.852] and associated AP of 0.804 [0.786, 0.820]. Compared to the current state-of-the-art approaches, our results suggest that the proposed adaptive ROI approach in texture analysis of subchondral bone can increase the diagnostic performance for detecting the presence of radiographic OA

Inverse Statistical Physics of Protein Sequences: A Key Issues Review

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e.~evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.Comment: 18 pages, 7 figure

Maximum entropy models capture melodic styles

We introduce a Maximum Entropy model able to capture the statistics of melodies in music. The model can be used to generate new melodies that emulate the style of the musical corpus which was used to train it. Instead of using the $n-$body interactions of $(n-1)-$order Markov models, traditionally used in automatic music generation, we use a $k-$nearest neighbour model with pairwise interactions only. In that way, we keep the number of parameters low and avoid over-fitting problems typical of Markov models. We show that long-range musical phrases don't need to be explicitly enforced using high-order Markov interactions, but can instead emerge from multiple, competing, pairwise interactions. We validate our Maximum Entropy model by contrasting how much the generated sequences capture the style of the original corpus without plagiarizing it. To this end we use a data-compression approach to discriminate the levels of borrowing and innovation featured by the artificial sequences. The results show that our modelling scheme outperforms both fixed-order and variable-order Markov models. This shows that, despite being based only on pairwise interactions, this Maximum Entropy scheme opens the possibility to generate musically sensible alterations of the original phrases, providing a way to generate innovation