Abstract The number of published metagenome assemblies is rapidly growing due to advances in sequencing technologies. However, sequencing errors, variable coverage, repetitive genomic regions, and other factors can produce misassemblies, which are challenging to detect for taxonomically novel genomic data. Assembly errors can affect all downstream analyses of the assemblies. Accuracy for the state of the art in reference-free misassembly prediction does not exceed an AUPRC of 0.57, and it is not clear how well these models generalize to real-world data. Here, we present the Residual neural network for Misassembled Contig identification (ResMiCo), a deep learning approach for reference-free identification of misassembled contigs. To develop ResMiCo, we first generated a training dataset of unprecedented size and complexity that can be used for further benchmarking and developments in the field. Through rigorous validation, we show that ResMiCo is substantially more accurate than the state of the art, and the model is robust to novel taxonomic diversity and varying assembly methods. ResMiCo estimated 4.7% misassembled contigs per metagenome across multiple real-world datasets. We demonstrate how ResMiCo can be used to optimize metagenome assembly hyperparameters to improve accuracy, instead of optimizing solely for contiguity. The accuracy, robustness, and ease-of-use of ResMiCo make the tool suitable for general quality control of metagenome assemblies and assembly methodology optimization.

Authors Olga Mineeva, Daniel Danciu, Bernhard Schölkopf, Ruth E. Ley, Gunnar Rätsch, Nicholas D. Youngblut

Submitted bioRxiv

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Abstract Decision making algorithms, in practice, are often trained on data that exhibits a variety of biases. Decision-makers often aim to take decisions based on some ground-truth target that is assumed or expected to be unbiased, i.e., equally distributed across socially salient groups. In many practical settings, the ground-truth cannot be directly observed, and instead, we have to rely on a biased proxy measure of the ground-truth, i.e., biased labels, in the data. In addition, data is often selectively labeled, i.e., even the biased labels are only observed for a small fraction of the data that received a positive decision. To overcome label and selection biases, recent work proposes to learn stochastic, exploring decision policies via i) online training of new policies at each time-step and ii) enforcing fairness as a constraint on performance. However, the existing approach uses only labeled data, disregarding a large amount of unlabeled data, and thereby suffers from high instability and variance in the learned decision policies at different times. In this paper, we propose a novel method based on a variational autoencoder for practical fair decision-making. Our method learns an unbiased data representation leveraging both labeled and unlabeled data and uses the representations to learn a policy in an online process. Using synthetic data, we empirically validate that our method converges to the optimal (fair) policy according to the ground-truth with low variance. In real-world experiments, we further show that our training approach not only offers a more stable learning process but also yields policies with higher fairness as well as utility than previous approaches.

Authors Miriam Rateike, Ayan Majumdar, Olga Mineeva, Krishna P. Gummadi, Isabel Valera

Submitted FAccT '22

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Abstract Abstract Motivation Methodological advances in metagenome assembly are rapidly increasing in the number of published metagenome assemblies. However, identifying misassemblies is challenging due to a lack of closely related reference genomes that can act as pseudo ground truth. Existing reference-free methods are no longer maintained, can make strong assumptions that may not hold across a diversity of research projects, and have not been validated on large-scale metagenome assemblies. Results We present DeepMAsED, a deep learning approach for identifying misassembled contigs without the need for reference genomes. Moreover, we provide an in silico pipeline for generating large-scale, realistic metagenome assemblies for comprehensive model training and testing. DeepMAsED accuracy substantially exceeds the state-of-the-art when applied to large and complex metagenome assemblies. Our model estimates a 1% contig misassembly rate in two recent large-scale metagenome assembly publications. Conclusions DeepMAsED accurately identifies misassemblies in metagenome-assembled contigs from a broad diversity of bacteria and archaea without the need for reference genomes or strong modeling assumptions. Running DeepMAsED is straight-forward, as well as is model re-training with our dataset generation pipeline. Therefore, DeepMAsED is a flexible misassembly classifier that can be applied to a wide range of metagenome assembly projects.

Authors Olga Mineeva, Mateo Rojas-Carulla, Ruth E Ley, Bernhard Schölkopf, Nicholas D Youngblut

Submitted Bioinformatics (Oxford, England)

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