Han Liu

Zhihan Zhou, Weimin Wu, Harrison Ho et al.

We introduce DNABERT-S, a tailored genome model that develops species-aware embeddings to naturally cluster and segregate DNA sequences of different species in the embedding space. Differentiating species from genomic sequences (i.e., DNA and RNA) is vital yet challenging, since many real-world species remain uncharacterized, lacking known genomes for reference. Embedding-based methods are therefore used to differentiate species in an unsupervised manner. DNABERT-S builds upon a pre-trained genome foundation model named DNABERT-2. To encourage effective embeddings to error-prone long-read DNA sequences, we introduce Manifold Instance Mixup (MI-Mix), a contrastive objective that mixes the hidden representations of DNA sequences at randomly selected layers and trains the model to recognize and differentiate these mixed proportions at the output layer. We further enhance it with the proposed Curriculum Contrastive Learning (C$^2$LR) strategy. Empirical results on 23 diverse datasets show DNABERT-S's effectiveness, especially in realistic label-scarce scenarios. For example, it identifies twice more species from a mixture of unlabeled genomic sequences, doubles the Adjusted Rand Index (ARI) in species clustering, and outperforms the top baseline's performance in 10-shot species classification with just a 2-shot training. Model, codes, and data are publicly available at \url{https://github.com/MAGICS-LAB/DNABERT_S}.

Pratik Dutta, Matthew Obusan, Rekha Sathian et al.

Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood. Despite recent advances in deep-learning genomic approaches, accurately predicting and prioritizing clinically relevant mutations in gene regulatory regions remains a major challenge. Here we introduce Deep VRegulome, a deep-learning method for prediction and interpretation of functionally disruptive variants in the human regulome, which combines 700 DNABERT fine-tuned models, trained on vast amounts of ENCODE gene regulatory regions, with variant scoring, motif analysis, attention-based visualization, and survival analysis. We showcase its application on TCGA glioblastoma WGS dataset in prioritizing survival-associated mutations and regulatory regions. The analysis identified 572 splice-disrupting and 9,837 transcription-factor binding site altering mutations occurring in greater than 10% of glioblastoma samples. Survival analysis linked 1352 mutations and 563 disrupted regulatory regions to patient outcomes, enabling stratification via non-coding mutation signatures. All the code, fine-tuned models, and an interactive data portal are publicly available.

Jaeyeon Jang, Diego Klabjan, Han Liu et al.

Real-time dynamic scheduling is a crucial but notoriously challenging task in modern manufacturing processes due to its high decision complexity. Recently, reinforcement learning (RL) has been gaining attention as an impactful technique to handle this challenge. However, classical RL methods typically rely on human-made dispatching rules, which are not suitable for large-scale factory-wide scheduling. To bridge this gap, this paper applies a leader-follower multi-agent RL (MARL) concept to obtain desired coordination after decomposing the scheduling problem into a set of sub-problems that are handled by each individual agent for scalability. We further strengthen the procedure by proposing a rule-based conversion algorithm to prevent catastrophic loss of production capacity due to an agent's error. Our experimental results demonstrate that the proposed model outperforms the state-of-the-art deep RL-based scheduling models in various aspects. Additionally, the proposed model provides the most robust scheduling performance to demand changes. Overall, the proposed MARL-based scheduling model presents a promising solution to the real-time scheduling problem, with potential applications in various manufacturing industries.

Kaiqing Zhang, Zhuoran Yang, Han Liu et al.

Despite the increasing interest in multi-agent reinforcement learning (MARL) in multiple communities, understanding its theoretical foundation has long been recognized as a challenging problem. In this work, we address this problem by providing a finite-sample analysis for decentralized batch MARL with networked agents. Specifically, we consider two decentralized MARL settings, where teams of agents are connected by time-varying communication networks, and either collaborate or compete in a zero-sum game setting, without any central controller. These settings cover many conventional MARL settings in the literature. For both settings, we develop batch MARL algorithms that can be implemented in a decentralized fashion, and quantify the finite-sample errors of the estimated action-value functions. Our error analysis captures how the function class, the number of samples within each iteration, and the number of iterations determine the statistical accuracy of the proposed algorithms. Our results, compared to the finite-sample bounds for single-agent RL, involve additional error terms caused by decentralized computation, which is inherent in our decentralized MARL setting. This work appears to be the first finite-sample analysis for batch MARL, a step towards rigorous theoretical understanding of general MARL algorithms in the finite-sample regime.

Yuan Cao, Matey Neykov, Han Liu

This paper studies structure detection problems in high temperature ferromagnetic (positive interaction only) Ising models. The goal is to distinguish whether the underlying graph is empty, i.e., the model consists of independent Rademacher variables, versus the alternative that the underlying graph contains a subgraph of a certain structure. We give matching upper and lower minimax bounds under which testing this problem is possible/impossible respectively. Our results reveal that a key quantity called graph arboricity drives the testability of the problem. On the computational front, under a conjecture of the computational hardness of sparse principal component analysis, we prove that, unless the signal is strong enough, there are no polynomial time tests which are capable of testing this problem. In order to prove this result we exhibit a way to give sharp inequalities for the even moments of sums of i.i.d. Rademacher random variables which may be of independent interest.