Artificial Intelligence for Reducing Workload in Breast Cancer Screening with Digital Breast Tomosynthesis.

Background Digital breast tomosynthesis (DBT) has higher diagnostic accuracy than digital mammography, but interpretation time is substantially longer. Artificial intelligence (AI) could improve reading efficiency. Purpose To evaluate the use of AI to reduce workload by filtering out normal DBT screens. Materials and Methods The retrospective study included 13 306 DBT examinations from 9919 women performed between June 2013 and November 2018 from two health care networks. The cohort was split into training, validation, and test sets (3948, 1661, and 4310 women, respectively). A workflow was simulated in which the AI model classified cancer-free examinations that could be dismissed from the screening worklist and used the original radiologists' interpretations on the rest of the worklist examinations. The AI system was also evaluated with a reader study of five breast radiologists reading the DBT mammograms of 205 women. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and recall rate were evaluated in both studies. Statistics were computed across 10 000 bootstrap samples to assess 95% CIs, noninferiority, and superiority tests. Results The model was tested on 4310 screened women (mean age, 60 years ± 11 [standard deviation]; 5182 DBT examinations). Compared with the radiologists' performance (417 of 459 detected cancers [90.8%], 477 recalls in 5182 examinations [9.2%]), the use of AI to automatically filter out cases would result in 39.6% less workload, noninferior sensitivity (413 of 459 detected cancers; 90.0%; P = .002), and 25% lower recall rate (358 recalls in 5182 examinations; 6.9%; P = .002). In the reader study, AUC was higher in the standalone AI compared with the mean reader (0.84 vs 0.81; P = .002). Conclusion The artificial intelligence model was able to identify normal digital breast tomosynthesis screening examinations, which decreased the number of examinations that required radiologist interpretation in a simulated clinical workflow. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Leveraging Comprehensive Health Records for Breast Cancer Risk Prediction: A Binational Assessment.

Breast cancer (BC) risk models based on electronic health records (EHR) can assist physicians in estimating the probability of an individual with certain risk factors to develop BC in the future. In this retrospective study, we used clinical data combined with machine learning tools to assess the utility of a personalized BC risk model on 13,786 Israeli and 1,695 American women who underwent screening mammography in the years 2012-2018 and 2008-2018, respectively. Clinical features were extracted from EHR, personal questionnaires, and past radiologists' reports. Using a set of 1,547 features, the predictive ability for BC within 12 months was measured in both datasets and in sub-cohorts of interest. Our results highlight the improved performance of our model over previous established BC risk models, their ultimate potential for risk-based screening policies on first time patients and novel clinically relevant risk factors that can compensate for the absence of imaging history information.

ExpaRNA-P: simultaneous exact pattern matching and folding of RNAs.

BACKGROUND: Identifying sequence-structure motifs common to two RNAs can speed up the comparison of structural RNAs substantially. The core algorithm of the existent approach ExpaRNA solves this problem for a priori known input structures. However, such structures are rarely known; moreover, predicting them computationally is no rescue, since single sequence structure prediction is highly unreliable. RESULTS: The novel algorithm ExpaRNA-P computes exactly matching sequence-structure motifs in entire Boltzmann-distributed structure ensembles of two RNAs; thereby we match and fold RNAs simultaneously, analogous to the well-known "simultaneous alignment and folding" of RNAs. While this implies much higher flexibility compared to ExpaRNA, ExpaRNA-P has the same very low complexity (quadratic in time and space), which is enabled by its novel structure ensemble-based sparsification. Furthermore, we devise a generalized chaining algorithm to compute compatible subsets of ExpaRNA-P's sequence-structure motifs. Resulting in the very fast RNA alignment approach ExpLoc-P, we utilize the best chain as anchor constraints for the sequence-structure alignment tool LocARNA. ExpLoc-P is benchmarked in several variants and versus state-of-the-art approaches. In particular, we formally introduce and evaluate strict and relaxed variants of the problem; the latter makes the approach sensitive to compensatory mutations. Across a benchmark set of typical non-coding RNAs, ExpLoc-P has similar accuracy to LocARNA but is four times faster (in both variants), while it achieves a speed-up over 30-fold for the longest benchmark sequences (≈400nt). Finally, different ExpLoc-P variants enable tailoring of the method to specific application scenarios. ExpaRNA-P and ExpLoc-P are distributed as part of the LocARNA package. The source code is freely available at http://www.bioinf.uni-freiburg.de/Software/ExpaRNA-P . CONCLUSIONS: ExpaRNA-P's novel ensemble-based sparsification reduces its complexity to quadratic time and space. Thereby, ExpaRNA-P significantly speeds up sequence-structure alignment while maintaining the alignment quality. Different ExpaRNA-P variants support a wide range of applications.

Local Exact Pattern Matching for Non-Fixed RNA Structures.

Detecting local common sequence-structure regions of RNAs is a biologically important problem. Detecting such regions allows biologists to identify functionally relevant similarities between the inspected molecules. We developed dynamic programming algorithms for finding common structure-sequence patterns between two RNAs. The RNAs are given by their sequence and a set of potential base pairs with associated probabilities. In contrast to prior work on local pattern matching of RNAs, we support the breaking of arcs. This allows us to add flexibility over matching only fixed structures; potentially matching only a similar subset of specified base pairs. We present an O(n(3)) algorithm for local exact pattern matching between two nested RNAs, and an O(n(3) log n) algorithm for one nested RNA and one bounded-unlimited RNA. In addition, an algorithm for approximate pattern matching is introduced that for two given nested RNAs and a number k, finds the maximal local pattern matching score between the two RNAs with at most k mismatches in O(n(3)k(2)) time. Finally, we present an O(n(3)) algorithm for finding the most similar subforest between two nested RNAs.