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Biology subjects

Mew, N. C.

Publications and source records attributed to Mew, N. C..

2 recordsLinked to original sources

Deep learning from multiple experts improves identification of amyloid neuropathologies

Pathologists can label pathologies differently, making it challenging to yield consistent assessments in the absence of one ground truth. To address this problem, we present a DL approach that draws on a cohort of experts, weighs each contribution, and is robust to noisy labels. We collected 100,495 annotations on 20,099 candidate amyloid beta neuropathologies (cerebral amyloid angiopathy (CAA), and cored and diffuse plaques) from three institutions, independently annotated by five experts. DL methods trained on a consensus-of-two strategy yielded 12.6-26% improvements by area under the precision recall curve (AUPRC) when compared to those that learned individualized annotations. This strategy surpassed individual-expert models, even when unfairly assessed on benchmarks favoring them. Moreover, ensembling over individual models was robust to hidden random annotators. In blind prospective tests of 52,555 subsequent expert-annotated images, the models labeled pathologies like their human counterparts (consensus model AUPRC=0.74 cored; 0.69 CAA). This study demonstrates a means to combine multiple ground truths into a common-ground DL model that yields consistent diagnoses informed by multiple and potentially variable expert opinion.

pathology↗

Adding stochastic negative examples into machine learning improves molecular bioactivity prediction

Multitask deep neural networks learn to predict ligand-target binding by example, yet public pharmacological datasets are sparse, imbalanced, and approximate. We constructed two hold-out benchmarks to approximate temporal and drug-screening test scenarios whose characteristics differ from a random split of conventional training datasets. We developed a pharmacological dataset augmentation procedure, Stochastic Negative Addition (SNA), that randomly assigns untested molecule-target pairs as transient negative examples during training. Under the SNA procedure, ligand drug-screening benchmark performance increases from R2 = 0.1926 {+/-} 0.0186 to 0.4269{+/-}0.0272 (121.7%). This gain was accompanied by a modest decrease in the temporal benchmark (13.42%). SNA increases in drug-screening performance were consistent for classification and regression tasks and outperformed scrambled controls. Our results highlight where data and feature uncertainty may be problematic, but also show how leveraging uncertainty into training improves predictions of drug-target relationships.

bioinformatics↗