MOTIVATION: Gene-disease associations are fundamental for understanding disease etiology and developing effective interventions and treatments. Identifying genes not yet associated with a disease due to a lack of studies is a challenging task in which prioritization based on prior knowledge is an important element. The computational search for new candidate disease genes may be eased by positive-unlabeled learning, the machine learning (ML) setting in which only a subset of instances are labeled as positive while the rest of the dataset is unlabeled. In this work, we propose a set of effective network-based features to be used in a novel Markov diffusion-based multi-class labeling strategy for putative disease gene discovery. RESULTS: The performances of the new labeling algorithm and the effectiveness of the proposed features have been tested on 10 different disease datasets using three ML algorithms. The new features have been compared against classical topological and functional/ontological features and a set of network- and biological-derived features already used in gene discovery tasks. The predictive power of the integrated methodology in searching for new disease genes has been found to be competitive against state-of-the-art algorithms. AVAILABILITY AND IMPLEMENTATION: The source code of NIAPU can be accessed at https://github.com/AndMastro/NIAPU. The source data used in this study are available online on the respective websites. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.