Methods and systems for tissue classification of a tissue sample are provided. The methods and systems transform the tissue image data to a biomarker enhanced tissue network (BETN) such that an individual cell or a sub-cellular structure in the tissue image data corresponds to a node in the BETN, define a feature vector based on a feature set representative of a tissue type of interest, cluster nodes of the BETN based on a similarity criterion of one or features of the feature vector, and classify the nodes in the tissue image data based on the grouping of the nodes of the BETN.