Statistical learning on biological data can be challenging due to confounding variables in sample collection and processing. Confounders can cause models to generalize poorly and result in inaccurate prediction performance metrics if models are not validated thoroughly. In this paper, we propose methods to control for confounding factors and further improve prediction performance. We introduce OrthoNormal basis construction In cOnfounding factor Normalization (ONION) to remove confounding covariates and use the Domain-Adversarial Neural Network (DANN) to penalize models for encoding confounder information. We apply the proposed methods to simulated and empirical patient data and show significant improvements in generalization.

High-dimensional data acquired from biological experiments such as next generation sequencing are subject to a number of confounding effects. These effects include both technical effects, such as variation across batches from instrument noise or sample processing, or institution-specific differences in sample acquisition and physical handling, as well as biological effects arising from true but irrelevant differences in the biology of each sample, such as age biases in diseases. Prior work has used linear methods to adjust for such batch effects. Here, we apply contrastive metric learning by a non-linear triplet network to optimize the ability to distinguish biologically distinct sample classes in the presence of irrelevant technical and biological variation. Using whole-genome cell-free DNA data from 817 patients, we demonstrate that our approach, METric learning for Confounder Control (METCC), is able to match or exceed the classification performance achieved using a best-in-class linear method (HCP) or no normalization. Critically, results from METCC appear less confounded by irrelevant technical variables like institution and batch than those from other methods even without access to high quality metadata information required by many existing techniques; offering hope for improved generalization.

In this paper we document our experiences with developing speech recognition for medical transcription - a system that automatically transcribes doctor-patient conversations. Towards this goal, we built a system along two different methodological lines - a Connectionist Temporal Classification (CTC) phoneme based model and a Listen Attend and Spell (LAS) grapheme based model. To train these models we used a corpus of anonymized conversations representing approximately 14,000 hours of speech. Because of noisy transcripts and alignments in the corpus, a significant amount of effort was invested in data cleaning issues. We describe a two-stage strategy we followed for segmenting the data. The data cleanup and development of a matched language model was essential to the success of the CTC based models. The LAS based models, however were found to be resilient to alignment and transcript noise and did not require the use of language models. CTC models were able to achieve a word error rate of 20.1%, and the LAS models were able to achieve 18.3%. Our analysis shows that both models perform well on important medical utterances and therefore can be practical for transcribing medical conversations.