Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data.

Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data. High-throughput sequencing technologies generate enormous amounts of short fragments (reads) which essentially oversample components of a mixture; the representation redundancy enables reconstruction of the components (haplotypes, viral strains). The reconstruction problem, known to be NP-hard, boils down to grouping together reads originating from the same component in a mixture. Existing methods struggle to solve this problem with required level of accuracy and low runtimes; the problem is becoming increasingly more challenging as the number and length of the components increase. This paper proposes a read clustering method based on a convolutional auto-encoder designed to first project sequenced fragments to a low-dimensional space and then estimate the probability of the read origin using learned embedded features. The components are reconstructed by finding consensus sequences that agglomerate reads from the same origin. Mini-batch stochastic gradient descent and dimension reduction of reads allow the proposed method to efficiently deal with massive numbers of long reads. Experiments on simulated, semi-experimental and experimental data demonstrate the ability of the proposed method to accurately reconstruct haplotypes and viral quasispecies, often demonstrating superior performance compared to state-of-the-art methods. Source codes are available at https://github.com/WuLoli/CAECseq.

Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data.

Weaknesses: As noted below, (1) it is not clear what the contribution of their method is, and (2) necessary details are missing from their evaluations. Also, at some points of their approach in preparing the dataset, they used some restrictions on some parameters but they didn't mention why they used these numbers. This is concerning, so I think they need to clarify why they used those parameters. For example, for TB they mention that: "Read alignment is performed using BWA-MEM (Li and Durbin, 2009), where the reads with mapping scores lower than 40 are filtered out for quality control." But for HIV they choose different approach: "Reads with mapping score lower than 60 and length shorter than 150 bp are filtered out for quality control".

All referees vote for acceptance, and I also fully support this point of view, although the methodological contribution might be somewhat limited. However, it is a very solid application paper.

Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data. High-throughput sequencing technologies generate enormous amounts of short fragments (reads) which essentially oversample components of a mixture; the representation redundancy enables reconstruction of the components (haplotypes, viral strains). The reconstruction problem, known to be NP-hard, boils down to grouping together reads originating from the same component in a mixture. Existing methods struggle to solve this problem with required level of accuracy and low runtimes; the problem is becoming increasingly more challenging as the number and length of the components increase. This paper proposes a read clustering method based on a convolutional auto-encoder designed to first project sequenced fragments to a low-dimensional space and then estimate the probability of the read origin using learned embedded features.

In explainable artificial intelligence, discriminative feature localization is critical to reveal a blackbox model's decision-making process from raw data to prediction. In this article, we use two real datasets, the MNIST handwritten digits and MIT-BIH Electrocardiogram (ECG) signals, to motivate key characteristics of discriminative features, namely adaptiveness, predictive importance and effectiveness. Then, we develop a localization framework based on adversarial attacks to effectively localize discriminative features. In contrast to existing heuristic methods, we also provide a statistically guaranteed interpretability of the localized features by measuring a generalized partial $R^2$. We apply the proposed method to the MNIST dataset and the MIT-BIH dataset with a convolutional auto-encoder. In the first, the compact image regions localized by the proposed method are visually appealing. Similarly, in the second, the identified ECG features are biologically plausible and consistent with cardiac electrophysiological principles while locating subtle anomalies in a QRS complex that may not be discernible by the naked eye. Overall, the proposed method compares favorably with state-of-the-art competitors. Accompanying this paper is a Python library dnn-locate (https://dnn-locate.readthedocs.io/en/latest/) that implements the proposed approach.

Feature selection aims to select a subset of features to optimize the performances of downstream predictive tasks. Recently, multi-agent reinforced feature selection (MARFS) has been introduced to automate feature selection, by creating agents for each feature to select or deselect corresponding features. Although MARFS enjoys the automation of the selection process, MARFS suffers from not just the data complexity in terms of contents and dimensionality, but also the exponentially-increasing computational costs with regard to the number of agents. The raised concern leads to a new research question: Can we simplify the selection process of agents under reinforcement learning context so as to improve the efficiency and costs of feature selection? To address the question, we develop a single-agent reinforced feature selection approach integrated with restructured choice strategy. Specifically, the restructured choice strategy includes: 1) we exploit only one single agent to handle the selection task of multiple features, instead of using multiple agents. 2) we develop a scanning method to empower the single agent to make multiple selection/deselection decisions in each round of scanning. 3) we exploit the relevance to predictive labels of features to prioritize the scanning orders of the agent for multiple features. 4) we propose a convolutional auto-encoder algorithm, integrated with the encoded index information of features, to improve state representation. 5) we design a reward scheme that take into account both prediction accuracy and feature redundancy to facilitate the exploration process. Finally, we present extensive experimental results to demonstrate the efficiency and effectiveness of the proposed method.