Dataset Information

SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with high generalization performance.

ABSTRACT: We evaluated SpCas9 activities at 12,832 target sequences using a high-throughput approach based on a human cell library containing single-guide RNA-encoding and target sequence pairs. Deep learning-based training on this large dataset of SpCas9-induced indel frequencies led to the development of a SpCas9 activity-predicting model named DeepSpCas9. When tested against independently generated datasets (our own and those published by other groups), DeepSpCas9 showed high generalization performance. DeepSpCas9 is available at http://deepcrispr.info/DeepSpCas9.

SUBMITTER: Kim HK

PROVIDER: S-EPMC6834390 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with high generalization performance.

Kim Hui Kwon HK Kim Younggwang Y Lee Sungtae S Min Seonwoo S Bae Jung Yoon JY Choi Jae Woo JW Park Jinman J Jung Dongmin D Yoon Sungroh S Kim Hyongbum Henry HH

Science advances 20191106 11

We evaluated SpCas9 activities at 12,832 target sequences using a high-throughput approach based on a human cell library containing single-guide RNA-encoding and target sequence pairs. Deep learning-based training on this large dataset of SpCas9-induced indel frequencies led to the development of a SpCas9 activity-predicting model named DeepSpCas9. When tested against independently generated datasets (our own and those published by other groups), DeepSpCas9 showed high generalization performance ...[more]

PMID: 31723604

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Project description:BackgroundThere is interest in using convolutional neural networks (CNNs) to analyze medical imaging to provide computer-aided diagnosis (CAD). Recent work has suggested that image classification CNNs may not generalize to new data as well as previously believed. We assessed how well CNNs generalized across three hospital systems for a simulated pneumonia screening task.Methods and findingsA cross-sectional design with multiple model training cohorts was used to evaluate model generalizability to external sites using split-sample validation. A total of 158,323 chest radiographs were drawn from three institutions: National Institutes of Health Clinical Center (NIH; 112,120 from 30,805 patients), Mount Sinai Hospital (MSH; 42,396 from 12,904 patients), and Indiana University Network for Patient Care (IU; 3,807 from 3,683 patients). These patient populations had an age mean (SD) of 46.9 years (16.6), 63.2 years (16.5), and 49.6 years (17) with a female percentage of 43.5%, 44.8%, and 57.3%, respectively. We assessed individual models using the area under the receiver operating characteristic curve (AUC) for radiographic findings consistent with pneumonia and compared performance on different test sets with DeLong's test. The prevalence of pneumonia was high enough at MSH (34.2%) relative to NIH and IU (1.2% and 1.0%) that merely sorting by hospital system achieved an AUC of 0.861 (95% CI 0.855-0.866) on the joint MSH-NIH dataset. Models trained on data from either NIH or MSH had equivalent performance on IU (P values 0.580 and 0.273, respectively) and inferior performance on data from each other relative to an internal test set (i.e., new data from within the hospital system used for training data; P values both <0.001). The highest internal performance was achieved by combining training and test data from MSH and NIH (AUC 0.931, 95% CI 0.927-0.936), but this model demonstrated significantly lower external performance at IU (AUC 0.815, 95% CI 0.745-0.885, P = 0.001). To test the effect of pooling data from sites with disparate pneumonia prevalence, we used stratified subsampling to generate MSH-NIH cohorts that only differed in disease prevalence between training data sites. When both training data sites had the same pneumonia prevalence, the model performed consistently on external IU data (P = 0.88). When a 10-fold difference in pneumonia rate was introduced between sites, internal test performance improved compared to the balanced model (10× MSH risk P < 0.001; 10× NIH P = 0.002), but this outperformance failed to generalize to IU (MSH 10× P < 0.001; NIH 10× P = 0.027). CNNs were able to directly detect hospital system of a radiograph for 99.95% NIH (22,050/22,062) and 99.98% MSH (8,386/8,388) radiographs. The primary limitation of our approach and the available public data is that we cannot fully assess what other factors might be contributing to hospital system-specific biases.ConclusionPneumonia-screening CNNs achieved better internal than external performance in 3 out of 5 natural comparisons. When models were trained on pooled data from sites with different pneumonia prevalence, they performed better on new pooled data from these sites but not on external data. CNNs robustly identified hospital system and department within a hospital, which can have large differences in disease burden and may confound predictions.

Dataset Information

SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with high generalization performance.

Publications

SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with high generalization performance.

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