The functional linkage network (FLN) construction is a primary and important step in drug discovery and disease gene prioritization methods. In order to construct FLN, several methods have been introduced based on integration of various biological data. Although, there are impressive ideas behind these methods, they suffer from low quality of the biological data. In this paper, a hierarchical sequence-based approach is proposed to construct FLN. The proposed approach, denoted as S-FLN (Sequence-based Functional Linkage Network), uses the sequence of proteins as the primary data in three main steps. Firstly, the physicochemical properties of amino-acids are employed to describe the functionality of proteins. As the sequence of proteins is a more comprehensive and accurate primary data, more reliable relations are achieved. Secondly, seven different descriptor methods are used to extract feature vectors …