  Pulmonary Embolism (PE) is a common and potentially lethal condition. Most
patients die within the first few hours from the event. Despite diagnostic
advances, delays and underdiagnosis in PE are common.To increase the diagnostic
performance in PE, current diagnostic work-up of patients with suspected acute
pulmonary embolism usually starts with the assessment of clinical pretest
probability using plasma d-Dimer measurement and clinical prediction rules. The
most validated and widely used clinical decision rules are the Wells and Geneva
Revised scores. We aimed to develop a new clinical prediction rule (CPR) for PE
based on topological data analysis and artificial neural network. Filter or
wrapper methods for features reduction cannot be applied to our dataset: the
application of these algorithms can only be performed on datasets without
missing data. Instead, we applied Topological data analysis (TDA) to overcome
the hurdle of processing datasets with null values missing data. A topological
network was developed using the Iris software (Ayasdi, Inc., Palo Alto). The PE
patient topology identified two ares in the pathological group and hence two
distinct clusters of PE patient populations. Additionally, the topological
netowrk detected several sub-groups among healthy patients that likely are
affected with non-PE diseases. TDA was further utilized to identify key
features which are best associated as diagnostic factors for PE and used this
information to define the input space for a back-propagation artificial neural
network (BP-ANN). It is shown that the area under curve (AUC) of BP-ANN is
greater than the AUCs of the scores (Wells and revised Geneva) used among
physicians. The results demonstrate topological data analysis and the BP-ANN,
when used in combination, can produce better predictive models than Wells or
revised Geneva scores system for the analyzed cohort
