Objective A major bottleneck hindering utilization of electronic health record data for translational research is the lack of precise phenotype labels. Chart review as well as rule-based and supervised phenotyping approaches require laborious expert input, hampering applicability to studies that require many phenotypes to be defined and labeled de novo. Though International Classification of Diseases codes are often used as surrogates for true labels in this setting, these sometimes suffer from poor specificity. We propose a fully automated topic modeling algorithm to simultaneously annotate multiple phenotypes. Materials and Methods Surrogate-guided ensemble latent Dirichlet allocation (sureLDA) is a label-free multidimensional phenotyping method. It first uses the PheNorm algorithm to initialize probabilities based on 2 surrogate features for each target phenotype, and then leverages these probabilities to constrain the LDA topic model to generate phenotype-specific topics. Finally, it combines phenotype-feature counts with surrogates via clustering ensemble to yield final phenotype probabilities. Results sureLDA achieves reliably high accuracy and precision across a range of simulated and real-world phenotypes. Its performance is robust to phenotype prevalence and relative informativeness of surogate vs nonsurrogate features. It also exhibits powerful feature selection properties. Discussion sureLDA combines attractive properties of PheNorm and LDA to achieve high accuracy and precision robust to diverse phenotype characteristics. It offers particular improvement for phenotypes insufficiently captured by a few surrogate features. Moreover, sureLDA’s feature selection ability enables it to handle high feature dimensions and produce interpretable computational phenotypes. Conclusions sureLDA is well suited toward large-scale electronic health record phenotyping for highly multiphenotype applications such as phenome-wide association studies .

The increasing availability of electronic health record (EHR) systems has created enormous potential for translational research. However, it is difficult to know all the relevant codes related to a phenotype due to the large number of codes available. Traditional data mining approaches often require the use of patient-level data, which hinders the ability to share data across institutions. In this project, we demonstrate that multi-center large-scale code embeddings can be used to efficiently identify relevant features related to a disease of interest. We constructed large-scale code embeddings for a wide range of codified concepts from EHRs from two large medical centers. We developed knowledge extraction via sparse embedding regression (KESER) for feature selection and integrative network analysis. We evaluated the quality of the code embeddings and assessed the performance of KESER in feature selection for eight diseases. Besides, we developed an integrated clinical knowledge map combining embedding data from both institutions. The features selected by KESER were comprehensive compared to lists of codified data generated by domain experts. Features identified via KESER resulted in comparable performance to those built upon features selected manually or with patient-level data. The knowledge map created using an integrative analysis identified disease-disease and disease-drug pairs more accurately compared to those identified using single institution data. Analysis of code embeddings via KESER can effectively reveal clinical knowledge and infer relatedness among codified concepts. KESER bypasses the need for patient-level data in individual analyses providing a significant advance in enabling multi-center studies using EHR data.

A bio-inspired approach for efficient conversion of cellulose to formic acid (FA) was developed in an aqueous alkaline medium. Metalloporphyrins mimicking cytochrome P450 exhibit efficiently and selectively catalytic performance in catalytic conversion of cellulose. High yield of FA about 63.7% was obtained by using sulfonated iron(III) porphyrin as the catalyst and O 2 as the oxidant. Iron(III)-peroxo species, TSPPFe III OO  , was involved to cleave the C-C bonds of gluconic acid to FA in this catalytic system. This approach used relatively high concentration of cellulose and ppm concentration of catalyst. This work may provide a bio-inspired route to efficient conversion of cellulose to FA.

We propose double/debiased machine learning approaches to infer (at the parametric rate n −1/2 ) the parametric component of a logistic partially linear model with the binary response following a conditional logistic model of a low dimensional linear parametric function of some key (exposure) covariates and a nonparametric function adjusting for the confounding effect of other covariates. We consider a Neyman orthogonal (doubly robust) score equation consisting of two nuisance functions: nonparametric component in the logistic model and conditional mean of the exposure on the other covariates and with the response fixed. To estimate the nuisance models, we separately consider the use of high dimensional (HD) sparse parametric models and more general (typically nonparametric) machine learning (ML) methods. In the HD case, we derive certain moment equations to calibrate the first order bias of the nuisance models and grant our method a model double robustness property in the sense that our estimator achieves the desirable O(n −1/2 ) rate when at least one of the nuisance models is correctly specified and both of them are ultra-sparse. In the ML case, the non-linearity of the logit link makes it substantially harder than the partially linear setting to use an arbitrary conditional mean learning algorithm to estimate nuisance component of the logistic model. We handle this obstacle through a novel "full model refitting" procedure that is easy-to-implement and facilitates the use of nonparametric ML algorithms in our framework. Our ML estimator is rate doubly robust in the same sense as Chernozhukov et al. (2018a). We evaluate our methods through simulation studies and apply them in assessing the effect of emergency contraceptive (EC) pill on early gestation foetal with a policy reform in Chile in 2008 (Bentancor and Clarke, 2017).