The off‐target effects induced by guide RNAs in the CRISPR/Cas9 gene‐editing system have raised substantial concerns in recent years. Many in silico predictive models have been developed for predicting the off‐target activities; however, few are capable of predicting the off‐target activities with insertions or deletions between guide RNA and target DNA sequence pair. In order to fill this gap, a recurrent convolutional network named CRISPR‐Net is developed for scoring the gRNA‐target pairs with mismatches and indels; and a machine‐learning based model named CRISPR‐Net‐Aggregate is also developed for aggregating the scores as the consensus off‐target score for each potential guide RNA. It is demonstrated that CRISPR‐Net achieves competitive performance on CIRCLE‐Seq and GUIDE‐seq datasets with indels and mismatches, outperforming the state‐of‐the‐art off‐target prediction methods on two independent mismatch‐only datasets. The CRISPR‐Net‐Aggregate also surpasses a competing method on the aggregation task. Moreover, a two‐stage sensitivity analysis is introduced to visualize the CRISPR‐Net prediction on the gRNA‐target pair of interest, demonstrating how implicit knowledge encoded in CRISPR‐Net contributes to the accurate off‐target activity quantification. Finally, the source code is made available at the Code Ocean repository (https://codeocean.com/capsule/9553651/tree/v1).

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Summary The early detection of cancers has the potential to save many lives. A recent attempt has been demonstrated successful. However, we note several critical limitations. Given the central importance and broad impact of early cancer detection, we aspire to address those limitations. We explore different supervised learning approaches for multiple cancer type detection and observe significant improvements; for instance, one of our approaches (i.e., CancerA1DE) can double the existing sensitivity from 38% to 77% for the earliest cancer detection (i.e., Stage I) at the 99% specificity level. For Stage II, it can even reach up to about 90% across multiple cancer types. In addition, CancerA1DE can also double the existing sensitivity from 30% to 70% for detecting breast cancers at the 99% specificity level. Data and model analysis are conducted to reveal the underlying reasons. A website is built at http://cancer.cs.cityu.edu.hk/ .

Keloids are regarded as benign fibroproliferative diseases with unknown pathogenesis that only occur in humans. Keloid tissue proliferates abnormally and bulges beyond the edge of the skin lesion.Keloid tissue not only affects the appearance and causes pain and itching but also causes physical and mental illness in patients. 1 Keloids are characterized by fibroblast proliferation and excessive collagen deposition in the dermis. 2 Although several factors, such as hyperactive inflammation, genetic predisposition, cell heterogeneity and tension, have been shown to play crucial roles in keloid development, the pathogenesis of keloids is still unclear. 3,4 It has been reported that multiple signalling pathways are involved in the pathogenesis of keloids. For instance, the overactive TGFβ-SMAD signalling pathway is the most studied, and it stimulates collagen synthesis and fibroblast proliferation by interacting with