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Abstract: Shale gas gathering systems are of great importance in gas fields for the efficient and reliable transportation of gas. In traditional design methods, pipeline layouts are optimized only from an economic point of view, where reliability is evaluated after optimization. However, reliability can be enhanced by spare pipelines so that both economic and reliable aspects are evaluated simultaneously. Based on the idea of enhancing reliability, this research proposes a methodology for optimizing the pipeline layout problem including well clustering, stations site selecting, and piping. Different topology arrangements and spare pipelines are investigated to enhance the production efficiency and reliability of the pipeline network under earthquake-related uncertainties. Reliability evaluation is converted into an economic one so that the objective of this work is to minimize the total annual cost. To solve such a complex problem, genetic algorithm, K-means algorithm, GeoSteiner algorithm, Kruskal algorithm, linear programming and Monte Carlo simulations are combined. A real-world case study illustrates the effectiveness of the proposed methodology and shows a 36.53% reduction in the total annual cost compared with the initial scheme.