Heart failure (HF) is a leading cause of morbidity, mortality, and health care costs. Prolonged conduction through the myocardium can occur with HF, and a device-driven approach, termed cardiac resynchronization therapy (CRT), can improve left ventri
cular (LV) myocardial conduction patterns. While a functional benefit of CRT has been demonstrated, a large proportion of HF patients (30-50%) receiving CRT do not show sufficient improvement. Moreover, identifying HF patients that would benefit from CRT prospectively remains a clinical challenge. Accordingly, strategies to effectively predict those HF patients that would derive a functional benefit from CRT holds great medical and socio-economic importance. Thus, we used machine learning methods of classifying HF patients, namely Cluster Analysis, Decision Trees, and Artificial neural networks, to develop predictive models of individual outcomes following CRT. Clinical, functional, and biomarker data were collected in HF patients before and following CRT. A prospective 6-month endpoint of a reduction in LV volume was defined as a CRT response. Using this approach (418 responders, 412 non-responders), each with 56 parameters, we could classify HF patients based on their response to CRT with more than 95% success. We have demonstrated that using machine learning approaches can identify HF patients with a high probability of a positive CRT response (95% accuracy), and of equal importance, identify those HF patients that would not derive a functional benefit from CRT. Developing this approach into a clinical algorithm to assist in clinical decision-making regarding the use of CRT in HF patients would potentially improve outcomes and reduce health care costs.
This article introduces a novel protein structure alignment method (named TALI) based on the protein backbone torsion angle instead of the more traditional distance matrix. Because the structural alignment of the two proteins is based on the comparis
on of two sequences of numbers (backbone torsion angles), we can take advantage of a large number of well-developed methods such as Smith-Waterman or Needleman-Wunsch. Here we report the result of TALI in comparison to other structure alignment methods such as DALI, CE, and SSM ass well as sequence alignment based on PSI-BLAST. TALI demonstrated great success over all other methods in application to challenging proteins. TALI was more successful in recognizing remote structural homology. TALI also demonstrated an ability to identify structural homology between two proteins where the structural difference was due to a rotation of internal domains by nearly 180$^circ$.
