Han Liu

Zhihan Zhou, Yanrong Ji, Weijian Li et al.

Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates $36$ distinct datasets across $9$ tasks, with input lengths ranging from $70$ to $10000$. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with $21 \times$ fewer parameters and approximately $92 \times$ less GPU time in pre-training.

Han Liu, Yubo Fan, Ipek Oguz et al.

Automatic segmentation of vestibular schwannoma (VS) and cochlea from magnetic resonance imaging can facilitate VS treatment planning. Unsupervised segmentation methods have shown promising results without requiring the time-consuming and laborious manual labeling process. In this paper, we present an approach for VS and cochlea segmentation in an unsupervised domain adaptation setting. Specifically, we first develop a cross-site cross-modality unpaired image translation strategy to enrich the diversity of the synthesized data. Then, we devise a rule-based offline augmentation technique to further minimize the domain gap. Lastly, we adopt a self-configuring segmentation framework empowered by self-training to obtain the final results. On the CrossMoDA 2022 validation leaderboard, our method has achieved competitive VS and cochlea segmentation performance with mean Dice scores of 0.8178 $\pm$ 0.0803 and 0.8433 $\pm$ 0.0293, respectively.

Jiacheng Wang, Hao Li, Han Liu et al.

Automated segmentation of multiple sclerosis (MS) lesions from MRI scans is important to quantify disease progression. In recent years, convolutional neural networks (CNNs) have shown top performance for this task when a large amount of labeled data is available. However, the accuracy of CNNs suffers when dealing with few and/or sparsely labeled datasets. A potential solution is to leverage the information available in large public datasets in conjunction with a target dataset which only has limited labeled data. In this paper, we propose a training framework, SSL2 (self-supervised-semi-supervised), for multi-modality MS lesion segmentation with limited supervision. We adopt self-supervised learning to leverage the knowledge from large public 3T datasets to tackle the limitations of a small 7T target dataset. To leverage the information from unlabeled 7T data, we also evaluate state-of-the-art semi-supervised methods for other limited annotation settings, such as small labeled training size and sparse annotations. We use the shifted-window (Swin) transformer1 as our backbone network. The effectiveness of self-supervised and semi-supervised training strategies is evaluated in our in-house 7T MRI dataset. The results indicate that each strategy improves lesion segmentation for both limited training data size and for sparse labeling scenarios. The combined overall framework further improves the performance substantially compared to either of its components alone. Our proposed framework thus provides a promising solution for future data/label-hungry 7T MS studies.

Kean Ming Tan, Junwei Lu, Tong Zhang et al.

Neuroscientists have enjoyed much success in understanding brain functions by constructing brain connectivity networks using data collected under highly controlled experimental settings. However, these experimental settings bear little resemblance to our real-life experience in day-to-day interactions with the surroundings. To address this issue, neuroscientists have been measuring brain activity under natural viewing experiments in which the subjects are given continuous stimuli, such as watching a movie or listening to a story. The main challenge with this approach is that the measured signal consists of both the stimulus-induced signal, as well as intrinsic-neural and non-neuronal signals. By exploiting the experimental design, we propose to estimate stimulus-locked brain network by treating non-stimulus-induced signals as nuisance parameters. In many neuroscience applications, it is often important to identify brain regions that are connected to many other brain regions during cognitive process. We propose an inferential method to test whether the maximum degree of the estimated network is larger than a pre-specific number. We prove that the type I error can be controlled and that the power increases to one asymptotically. Simulation studies are conducted to assess the performance of our method. Finally, we analyze a functional magnetic resonance imaging dataset obtained under the Sherlock Holmes movie stimuli.

Yi Zhen, Lei Wang, Han Liu et al.

Objective: To validate and compare the performance of eight available deep learning architectures in grading the severity of glaucoma based on color fundus images. Materials and Methods: We retrospectively collected a dataset of 5978 fundus images and their glaucoma severities were annotated by the consensus of two experienced ophthalmologists. We preprocessed the images to generate global and local regions of interest (ROIs), namely the global field-of-view images and the local disc region images. We then divided the generated images into three independent sub-groups for training, validation, and testing purposes. With the datasets, eight convolutional neural networks (CNNs) (i.e., VGG16, VGG19, ResNet, DenseNet, InceptionV3, InceptionResNet, Xception, and NASNetMobile) were trained separately to grade glaucoma severity, and validated quantitatively using the area under the receiver operating characteristic (ROC) curve and the quadratic kappa score. Results: The CNNs, except VGG16 and VGG19, achieved average kappa scores of 80.36% and 78.22% when trained from scratch on global and local ROIs, and 85.29% and 82.72% when fine-tuned using the pre-trained weights, respectively. VGG16 and VGG19 achieved reasonable accuracy when trained from scratch, but they failed when using pre-trained weights for global and local ROIs. Among these CNNs, the DenseNet had the highest classification accuracy (i.e., 75.50%) based on pre-trained weights when using global ROIs, as compared to 65.50% when using local ROIs. Conclusion: The experiments demonstrated the feasibility of the deep learning technology in grading glaucoma severity. In particular, global field-of-view images contain relatively richer information that may be critical for glaucoma assessment, suggesting that we should use the entire field-of-view of a fundus image for training a deep learning network.

Cong Ma, Junwei Lu, Han Liu

We develop a new modeling framework for Inter-Subject Analysis (ISA). The goal of ISA is to explore the dependency structure between different subjects with the intra-subject dependency as nuisance. It has important applications in neuroscience to explore the functional connectivity between brain regions under natural stimuli. Our framework is based on the Gaussian graphical models, under which ISA can be converted to the problem of estimation and inference of the inter-subject precision matrix. The main statistical challenge is that we do not impose sparsity constraint on the whole precision matrix and we only assume the inter-subject part is sparse. For estimation, we propose to estimate an alternative parameter to get around the non-sparse issue and it can achieve asymptotic consistency even if the intra-subject dependency is dense. For inference, we propose an "untangle and chord" procedure to de-bias our estimator. It is valid without the sparsity assumption on the inverse Hessian of the log-likelihood function. This inferential method is general and can be applied to many other statistical problems, thus it is of independent theoretical interest. Numerical experiments on both simulated and brain imaging data validate our methods and theory.

Ethan X. Fang, Yang Ning, Han Liu

This paper proposes a decorrelation-based approach to test hypotheses and construct confidence intervals for the low dimensional component of high dimensional proportional hazards models. Motivated by the geometric projection principle, we propose new decorrelated score, Wald and partial likelihood ratio statistics. Without assuming model selection consistency, we prove the asymptotic normality of these test statistics, establish their semiparametric optimality. We also develop new procedures for constructing pointwise confidence intervals for the baseline hazard function and baseline survival function. Thorough numerical results are provided to back up our theory.

Huitong Qiu, Fang Han, Han Liu et al.

In this manuscript we consider the problem of jointly estimating multiple graphical models in high dimensions. We assume that the data are collected from n subjects, each of which consists of T possibly dependent observations. The graphical models of subjects vary, but are assumed to change smoothly corresponding to a measure of closeness between subjects. We propose a kernel based method for jointly estimating all graphical models. Theoretically, under a double asymptotic framework, where both (T,n) and the dimension d can increase, we provide the explicit rate of convergence in parameter estimation. It characterizes the strength one can borrow across different individuals and impact of data dependence on parameter estimation. Empirically, experiments on both synthetic and real resting state functional magnetic resonance imaging (rs-fMRI) data illustrate the effectiveness of the proposed method.