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From bacteria following simple chemical gradients to the brain distinguishing complex odour information, the ability to recognize molecular patterns is essential for biological organisms. This type of information-processing function has been implemented using DNA-based neural networks, but has been limited to the recognition of a set of no more than four patterns, each composed of four distinct DNA molecules. Winner-take-all computation has been suggested as a potential strategy for enhancing the capability of DNA-based neural networks. Compared to the linear-threshold circuits and Hopfield networks used previously, winner-take-all circuits are computationally more powerful, allow simpler molecular implementation and are not constrained by the number of patterns and their complexity, so both a large number of simple patterns and a small number of complex patterns can be recognized. Here we report a systematic implementation of winner-take-all neural networks based on DNA-strand-displacement reactions. We use a previously developed seesaw DNA gate motif, extended to include a simple and robust component that facilitates the cooperative hybridization that is involved in the process of selecting a ‘winner’. We show that with this extended seesaw motif DNA-based neural networks can classify patterns into up to nine categories. Each of these patterns consists of 20 distinct DNA molecules chosen from the set of 100 that represents the 100 bits in 10 × 10 patterns, with the 20 DNA molecules selected tracing one of the handwritten digits ‘1’ to ‘9’. The network successfully classified test patterns with up to 30 of the 100 bits flipped relative to the digit patterns ‘remembered’ during training, suggesting that molecular circuits can robustly accomplish the sophisticated task of classifying highly complex and noisy information on the basis of similarity to a memory.

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits., DNA circuits hold promise for advancing information-based molecular technologies, yet it is challenging to design and construct them in practice. Thubagere et al. build DNA strand displacement circuits using unpurified strands whose sequences are automatically generated from a user-friendly compiler.

Given the potential importance of marginal artery localization in automated registration in computed tomography colonography (CTC), we have devised a semi-automated method of marginal vessel detection employing sequential Monte Carlo tracking (also known as particle filtering tracking) by multiple cue fusion based on intensity, vesselness, organ detection, and minimum spanning tree information for poorly enhanced vessel segments. We then employed a random forest algorithm for intelligent cue fusion and decision making which achieved high sensitivity and robustness. After applying a vessel pruning procedure to the tracking results, we achieved statistically significantly improved precision compared to a baseline Hessian detection method (2.7% versus 75.2%, p < 0.001). This method also showed statistically significantly improved recall rate compared to a 2-cue baseline method using fewer vessel cues (30.7% versus 67.7%, p < 0.001). These results demonstrate that marginal artery localization on CTC is feasible by combining a discriminative classifier (i.e., random forest) with a sequential Monte Carlo tracking mechanism. In so doing, we present the effective application of an anatomical probability map to vessel pruning as well as a supplementary spatial coordinate system for colonic segmentation and registration when this task has been confounded by colon lumen collapse. Published by Elsevier B.V.

In clinical practice and medical imaging research , automated computer-aided detection (CADe) is an important tool. While many methods can achieve high sensitivities, they typically suffer from high false positives (FP) per patient. In this study, we describe a two-stage coarse-to-fine approach using CADe candidate generation systems that operate at high sensitivity rates (close to \(100\%\) recall). In a second stage, we reduce false positive numbers using state-of-the-art machine learning methods, namely deep convolutional neural networks (ConvNet). The ConvNets are trained to differentiate hard false positives from true-positives utilizing a set of 2D (two-dimensional) or 2.5D re-sampled views comprising random translations, rotations, and multi-scale observations around a candidate’s center coordinate. During the test phase, we apply the ConvNets on unseen patient data and aggregate all probability scores for lesions (or pathology). We found that this second stage is a highly selective classifier that is able to reject difficult false positives while retaining good sensitivity rates. The method was evaluated on three data sets (sclerotic metastases, lymph nodes, colonic polyps) with varying numbers patients (59, 176, and 1,186, respectively). Experiments show that the method is able to generalize to different applications and increasing data set sizes. Marked improvements are observed in all cases: sensitivities increased from 57 to 70%, from 43 to 77% and from 58 to 75% for sclerotic metastases, lymph nodes and colonic polyps, respectively, at low FP rates per patient (3 FPs/patient).

Automated computer-aided detection (CADe) in medical imaging has been an important tool in clinical practice and research. State-of-the-art methods often show high sensitivities but at the cost of high false-positives (FP) per patient rates. We design a two-tiered coarse-to-fine cascade framework that first operates a candidate generation system at sensitivities of $\sim$100% but at high FP levels. By leveraging existing CAD systems, coordinates of regions or volumes of interest (ROI or VOI) for lesion candidates are generated in this step and function as input for a second tier, which is our focus in this study. In this second stage, we generate $N$ 2D (two-dimensional) or 2.5D views via sampling through scale transformations, random translations and rotations with respect to each ROI's centroid coordinates. These random views are used to train deep convolutional neural network (ConvNet) classifiers. In testing, the trained ConvNets are employed to assign class (e.g., lesion, pathology) probabilities for a new set of $N$ random views that are then averaged at each ROI to compute a final per-candidate classification probability. This second tier behaves as a highly selective process to reject difficult false positives while preserving high sensitivities. The methods are evaluated on three different data sets with different numbers of patients: 59 patients for sclerotic metastases detection, 176 patients for lymph node detection, and 1,186 patients for colonic polyp detection. Experimental results show the ability of ConvNets to generalize well to different medical imaging CADe applications and scale elegantly to various data sets. Our proposed methods improve CADe performance markedly in all cases. CADe sensitivities improved from 57% to 70%, from 43% to 77% and from 58% to 75% at 3 FPs per patient for sclerotic metastases, lymph nodes and colonic polyps, respectively., Comment: 2D vs 2.5D vs 3D inputs and comparison to other standard classifiers such as SVM have been addressed by more experimentation and two completely new sections and figures. Results and Discussions have been updated accordingly

We propose a new method for detecting abdominal lymphadenopathy by utilizing a random forest statistical classifier to create voxel-level lymph node predictions, i.e. initial detection of enlarged lymph nodes. The framework permits the combination of multiple statistical lymph node descriptors and appropriate feature selection in order to improve lesion detection beyond traditional enhancement filters. We show that Hessian blobness measurements alone are inadequate for detecting lymph nodes in the abdominal cavity. Of the features tested here, intensity proved to be the most important predictor for lymph node classification. For initial detection, candidate lesions were extracted from the 3D prediction map generated by random forest. Statistical features describing intensity distribution, shape, and texture were calculated from each enlarged lymph node candidate. In the last step, a support vector machine (SVM) was trained and tested based on the calculated features from candidates and labels determined by two experienced radiologists. The computer-aided detection (CAD) system was tested on a dataset containing 30 patients with 119 enlarged lymph nodes. Our method achieved an AUC of 0.762±0.022 and a sensitivity of 79.8% with 15 false positives suggesting it can aid radiologists in finding enlarged lymph nodes.

Enlarged lymph nodes (LNs) can provide important information for cancer diagnosis, staging, and measuring treatment reactions, making automated detection a highly sought goal. In this paper, we propose a new algorithm representation of decomposing the LN detection problem into a set of 2D object detection subtasks on sampled CT slices, largely alleviating the curse of dimensionality issue. Our 2D detection can be effectively formulated as linear classification on a single image feature type of Histogram of Oriented Gradients (HOG), covering a moderate field-of-view of 45 by 45 voxels. We exploit both simple pooling and sparse linear fusion schemes to aggregate these 2D detection scores for the final 3D LN detection. In this manner, detection is more tractable and does not need to perform perfectly at instance level (as weak hypotheses) since our aggregation process will robustly harness collective information for LN detection. Two datasets (90 patients with 389 mediastinal LNs and 86 patients with 595 abdominal LNs) are used for validation. Cross-validation demonstrates 78.0% sensitivity at 6 false positives/volume (FP/vol.) (86.1% at 10 FP/vol.) and 73.1% sensitivity at 6 FP/vol. (87.2% at 10 FP/vol.), for the mediastinal and abdominal datasets respectively. Our results compare favorably to previous state-of-the-art methods.

Millions of people worldwide are afflicted with painfulosteoarthritis, which is characterized by degradationof articular cartilage found in major joints such as thehip or knee. Symptoms include inflammation, pain,and decreased mobility. Because cartilage has a limitedability to self-heal, researchers have focused efforts onmethods that trigger cartilage regeneration. Our approachis to develop an injectable, protein-based hydrogel withmechanical properties analogous to healthy articularcartilage. The hydrogel provides an environment for cellgrowth and stimulates new tissue formation. We utilizedrecombinant DNA technology to create multifunctional,elastomeric proteins. The recombinant proteins weredesigned with biologically active domains to influence cellbehavior and resilin structural domains that mimic thestiffness of native cartilage. Resilin, a protein found in thewing and leg joints of mosquitoes, provided inspiration forthe mechanical domain in the recombinant protein. Thenew resilin-based protein was expressed in E. coli bacteria.Forming hydrogels requires a large quantity of engineeredprotein, so parameters such as bacterial host, incubationtemperature, expression time, and induction method wereoptimized to increase the protein yield. Using salt toprecipitate the protein and exploiting resilin’s heat stability,27 mg/L of recombinant protein was recovered at 95%purity. The protein expression and purification protocolswere established by analyzing experimental samples onSDS-PAGE gels and by Western blotting. The mechanicalproperties and interactions with stem cells are currentlybeing evaluated to assess the potential of the resilin-basedhydrogel as a treatment for osteoarthritis.