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Haploinsufficiency, wherein a single allele is not enough to maintain normal functions, can lead to many diseases including cancers and neurodevelopmental disorders. Recently, computational methods for identifying haploinsufficiency have been developed. However, most of those computational methods suffer from study bias, experimental noise and instability, resulting in unsatisfactory identification of haploinsufficient genes. To address those challenges, we propose a deep forest model, called HaForest, to identify haploinsufficient genes. The multiscale scanning is proposed to extract local contextual representations from input features under Linear Discriminant Analysis. After that, the cascade forest structure is applied to obtain the concatenated features directly by integrating decision-tree-based forests. Meanwhile, to exploit the complex dependency structure among haploinsufficient genes, the LightGBM library is embedded into HaForest to reveal the highly expressive features. To validate the effectiveness of our method, we compared it to several computational methods and four deep learning algorithms on five epigenomic data sets. The results reveal that HaForest achieves superior performance over the other algorithms, demonstrating its unique and complementary performance in identifying haploinsufficient genes. The standalone tool is available at https://github.com/yangyn533/HaForest. [ABSTRACT FROM AUTHOR]

The identification of hidden responders is often an essential challenge in precision oncology. A recent attempt based on machine learning has been proposed for classifying aberrant pathway activity from multiomic cancer data. However, we note several critical limitations there, such as high-dimensionality, data sparsity and model performance. Given the central importance and broad impact of precision oncology, we propose nature-inspired deep Ras activation pan-cancer (NatDRAP), a deep neural network (DNN) model, to address those restrictions for the identification of hidden responders. In this study, we develop the nature-inspired deep learning model that integrates bulk RNA sequencing, copy number and mutation data from PanCanAltas to detect pan-cancer Ras pathway activation. In NatDRAP, we propose to synergize the nature-inspired artificial bee colony algorithm with different gradient-based optimizers in one framework for optimizing DNNs in a collaborative manner. Multiple experiments were conducted on 33 different cancer types across PanCanAtlas. The experimental results demonstrate that the proposed NatDRAP can provide superior performance over other benchmark methods with strong robustness towards diagnosing RAS aberrant pathway activity across different cancer types. In addition, gene ontology enrichment and pathological analysis are conducted to reveal novel insights into the RAS aberrant pathway activity identification and characterization. NatDRAP is written in Python and available at https://github.com/lixt314/NatDRAP1. [ABSTRACT FROM AUTHOR]