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Water distribution systems (WDSs) are considered inherently vulnerable to intentional and accidental contamination. The installation of a water quality sensor system (WQSS) represents a valid strategy for securing WDSs against contamination. This paper proposes a novel topological-based methodological approach for defining a suitable WQSS, by also addressing both the computational intractability of the problem as the size of the WDS increases and the assumption that sensors are wrongly modelled and positioned on WDS nodes, rather than along system pipes. The method is tested on the WDS of Parete (Italy) and the results demonstrate the significant detection efficiency of the defined WQSS.