Developing and validating predictive decision tree models from mining chemical structural fingerprints and high–throughput screening data in PubChem

<p>Abstract</p> <p>Background</p> <p>Recent advances in high-throughput screening (HTS) techniques and readily available compound libraries generated using combinatorial chemistry or derived from natural products enable the testing of millions of compounds in a matter of days. Due to the amount of information produced by HTS assays, it is a very challenging task to mine the HTS data for potential interest in drug development research. Computational approaches for the analysis of HTS results face great challenges due to the large quantity of information and significant amounts of erroneous data produced.</p> <p>Results</p> <p>In this study, Decision Trees (DT) based models were developed to discriminate compound bioactivities by using their chemical structure fingerprints provided in the PubChem system <url>http://pubchem.ncbi.nlm.nih.gov</url>. The DT models were examined for filtering biological activity data contained in four assays deposited in the PubChem Bioassay Database including assays tested for 5HT1a agonists, antagonists, and HIV-1 RT-RNase H inhibitors. The 10-fold Cross Validation (CV) sensitivity, specificity and Matthews Correlation Coefficient (MCC) for the models are 57.2~80.5%, 97.3~99.0%, 0.4~0.5 respectively. A further evaluation was also performed for DT models built for two independent bioassays, where inhibitors for the same HIV RNase target were screened using different compound libraries, this experiment yields enrichment factor of 4.4 and 9.7.</p> <p>Conclusion</p> <p>Our results suggest that the designed DT models can be used as a virtual screening technique as well as a complement to traditional approaches for hits selection.</p

Continuous-mixture Autoregressive Networks for efficient variational calculation of many-body systems

We develop deep autoregressive networks with multi channels to compute many-body systems with \emph{continuous} spin degrees of freedom directly. As a concrete example, we embed the two-dimensional XY model into the continuous-mixture networks and rediscover the Kosterlitz-Thouless (KT) phase transition on a periodic square lattice. Vortices characterizing the quasi-long range order are accurately detected by the autoregressive neural networks. By learning the microscopic probability distributions from the macroscopic thermal distribution, the neural networks compute the free energy directly and find that free vortices and anti-vortices emerge in the high-temperature regime. As a more precise evaluation, we compute the helicity modulus to determine the KT transition temperature. Although the training process becomes more time-consuming with larger lattice sizes, the training time remains unchanged around the KT transition temperature. The continuous-mixture autoregressive networks we developed thus can be potentially used to study other many-body systems with continuous degrees of freedom.Comment: rewrite the whole manuscript. 6 pages, 4 figures, comments welcom