Lei Xin

Lei Xin, Lintao Ye, George Chiu et al.

We consider the problem of learning the dynamics of a linear system when one has access to data generated by an auxiliary system that shares similar (but not identical) dynamics, in addition to data from the true system. We use a weighted least squares approach, and provide finite sample error bounds of the learned model as a function of the number of samples and various system parameters from the two systems as well as the weight assigned to the auxiliary data. We show that the auxiliary data can help to reduce the intrinsic system identification error due to noise, at the price of adding a portion of error that is due to the differences between the two system models. We further provide a data-dependent bound that is computable when some prior knowledge about the systems, such as upper bounds on noise levels and model difference, is available. This bound can also be used to determine the weight that should be assigned to the auxiliary data during the model training stage.

Lei Xin, George Chiu, Shreyas Sundaram

We study the problem of estimating an unknown parameter in a distributed and online manner. Existing work on distributed online learning typically either focuses on asymptotic analysis, or provides bounds on regret. However, these results may not directly translate into bounds on the error of the learned model after a finite number of time-steps. In this paper, we propose a distributed online estimation algorithm which enables each agent in a network to improve its estimation accuracy by communicating with neighbors. We provide non-asymptotic bounds on the estimation error, leveraging the statistical properties of the underlying model. Our analysis demonstrates a trade-off between estimation error and communication costs. Further, our analysis allows us to determine a time at which the communication can be stopped (due to the costs associated with communications), while meeting a desired estimation accuracy. We also provide a numerical example to validate our results.

Zheng Ma, Jiazhen Chen, Lei Xin et al.

The integration of deep learning approaches in biomedical research has been transformative, enabling breakthroughs in various applications. Despite these strides, its application in protein inference is impeded by the scarcity of extensively labeled datasets, a challenge compounded by the high costs and complexities of accurate protein annotation. In this study, we introduce GraphPI, a novel framework that treats protein inference as a node classification problem. We treat proteins as interconnected nodes within a protein-peptide-PSM graph, utilizing a Graph Neural Network-based architecture to elucidate their interrelations. To address label scarcity, we train the model on a set of unlabeled public protein datasets with pseudo-labels derived from an existing protein inference algorithm, enhanced by self-training to iteratively refine labels based on confidence scores. Contrary to prevalent methodologies necessitating dataset-specific training, our research illustrates that GraphPI, due to the well normalized nature of Percolator features, exhibits universal applicability without dataset-specific fine-tuning, a feature that not only mitigates the risk of overfitting but also enhances computational efficiency. Our empirical experiments reveal notable performance on various test datasets and deliver significantly reduced computation times compared to common protein inference algorithms.

Lei Xin, George Chiu, Shreyas Sundaram

The problem of online change point detection is to detect abrupt changes in properties of time series, ideally as soon as possible after those changes occur. Existing work on online change point detection either assumes i.i.d data, focuses on asymptotic analysis, does not present theoretical guarantees on the trade-off between detection accuracy and detection delay, or is only suitable for detecting single change points. In this work, we study the online change point detection problem for linear dynamical systems with unknown dynamics, where the data exhibits temporal correlations and the system could have multiple change points. We develop a data-dependent threshold that can be used in our test that allows one to achieve a pre-specified upper bound on the probability of making a false alarm. We further provide a finite-sample-based bound for the probability of detecting a change point. Our bound demonstrates how parameters used in our algorithm affect the detection probability and delay, and provides guidance on the minimum required time between changes to guarantee detection.

Ngoc Hieu Tran, Zachariah Levine, Lei Xin et al.

Proteins are the main workhorses of biological functions in a cell, a tissue, or an organism. Identification and quantification of proteins in a given sample, e.g. a cell type under normal/disease conditions, are fundamental tasks for the understanding of human health and disease. In this paper, we present DeepNovo, a deep learning-based tool to address the problem of protein identification from tandem mass spectrometry data. The idea was first proposed in the context of de novo peptide sequencing [1] in which convolutional neural networks and recurrent neural networks were applied to predict the amino acid sequence of a peptide from its spectrum, a similar task to generating a caption from an image. We further develop DeepNovo to perform sequence database search, the main technique for peptide identification that greatly benefits from numerous existing protein databases. We combine two modules de novo sequencing and database search into a single deep learning framework for peptide identification, and integrate de Bruijn graph assembly technique to offer a complete solution to reconstruct protein sequences from tandem mass spectrometry data. This paper describes a comprehensive protocol of DeepNovo for protein identification, including training neural network models, dynamic programming search, database querying, estimation of false discovery rate, and de Bruijn graph assembly. Training and testing data, model implementations, and comprehensive tutorials in form of IPython notebooks are available in our GitHub repository (https://github.com/nh2tran/DeepNovo).

Zhenglun Kong, Yize Li, Fanhu Zeng et al.

In Transformer architectures, tokens\textemdash discrete units derived from raw data\textemdash are formed by segmenting inputs into fixed-length chunks. Each token is then mapped to an embedding, enabling parallel attention computations while preserving the input's essential information. Due to the quadratic computational complexity of transformer self-attention mechanisms, token reduction has primarily been used as an efficiency strategy. This is especially true in single vision and language domains, where it helps balance computational costs, memory usage, and inference latency. Despite these advances, this paper argues that token reduction should transcend its traditional efficiency-oriented role in the era of large generative models. Instead, we position it as a fundamental principle in generative modeling, critically influencing both model architecture and broader applications. Specifically, we contend that across vision, language, and multimodal systems, token reduction can: (i) facilitate deeper multimodal integration and alignment, (ii) mitigate "overthinking" and hallucinations, (iii) maintain coherence over long inputs, and (iv) enhance training stability, etc. We reframe token reduction as more than an efficiency measure. By doing so, we outline promising future directions, including algorithm design, reinforcement learning-guided token reduction, token optimization for in-context learning, and broader ML and scientific domains. We highlight its potential to drive new model architectures and learning strategies that improve robustness, increase interpretability, and better align with the objectives of generative modeling.

Lei Xin, Yuhao Zheng, Ke Cheng et al.

Modeling long sequences of user behaviors has emerged as a critical frontier in generative recommendation. However, existing solutions face a dilemma: linear attention mechanisms achieve efficiency at the cost of retrieval precision due to limited state capacity, while softmax attention suffers from prohibitive computational overhead. To address this challenge, we propose HyTRec, a model featuring a Hybrid Attention architecture that explicitly decouples long-term stable preferences from short-term intent spikes. By assigning massive historical sequences to a linear attention branch and reserving a specialized softmax attention branch for recent interactions, our approach restores precise retrieval capabilities within industrial-scale contexts involving ten thousand interactions. To mitigate the lag in capturing rapid interest drifts within the linear layers, we furthermore design Temporal-Aware Delta Network (TADN) to dynamically upweight fresh behavioral signals while effectively suppressing historical noise. Empirical results on industrial-scale datasets confirm the superiority that our model maintains linear inference speed and outperforms strong baselines, notably delivering over 8% improvement in Hit Rate for users with ultra-long sequences with great efficiency.

Lei Xin, Baike She, Qi Dou et al.

The identification of a linear system model from data has wide applications in control theory. The existing work that provides finite sample guarantees for linear system identification typically uses data from a single long system trajectory under i.i.d. random inputs, and assumes that the underlying dynamics is truly linear. In contrast, we consider the problem of identifying a linearized model when the true underlying dynamics is nonlinear, given that there is a certain constraint on the region where one can initialize the experiments. We provide a multiple trajectories-based deterministic data acquisition algorithm followed by a regularized least squares algorithm, and provide a finite sample error bound on the learned linearized dynamics. Our error bound shows that one can consistently learn the linearized dynamics, and demonstrates a trade-off between the error due to nonlinearity and the error due to noise. We validate our results through numerical experiments, where we also show the potential insufficiency of linear system identification using a single trajectory with i.i.d. random inputs, when nonlinearity does exist.

Zheng Ma, Zeping Mao, Ruixue Zhang et al.

Data-Independent Acquisition (DIA) was introduced to improve sensitivity to cover all peptides in a range rather than only sampling high-intensity peaks as in Data-Dependent Acquisition (DDA) mass spectrometry. However, it is not very clear how useful DIA data is for de novo peptide sequencing as the DIA data are marred with coeluted peptides, high noises, and varying data quality. We present a new deep learning method DIANovo, and address each of these difficulties, and improves the previous established systems by a large margin, via equipping the model with a deeper understanding of coeluted DIA spectra. This paper also provides criteria about when DIA data could be used for de novo peptide sequencing and when not to by providing a comparison between DDA and DIA, in both de novo and database search mode. We find that while DIA excels with narrow isolation windows on older-generation instruments, it loses its advantage with wider windows. However, with Orbitrap Astral, DIA consistently outperforms DDA due to narrow window mode enabled. We also provide a theoretical explanation of this phenomenon, emphasizing the critical role of the signal-to-noise profile in the successful application of de novo sequencing.

Fatema Tuz Zohora, M Ziaur Rahman, Ngoc Hieu Tran et al.

A promising technique of discovering disease biomarkers is to measure the relative protein abundance in multiple biofluid samples through liquid chromatography with tandem mass spectrometry (LC-MS/MS) based quantitative proteomics. The key step involves peptide feature detection in LC-MS map, along with its charge and intensity. Existing heuristic algorithms suffer from inaccurate parameters since different settings of the parameters result in significantly different outcomes. Therefore, we propose PointIso, to serve the necessity of an automated system for peptide feature detection that is able to find out the proper parameters itself, and is easily adaptable to different types of datasets. It consists of an attention based scanning step for segmenting the multi-isotopic pattern of peptide features along with charge and a sequence classification step for grouping those isotopes into potential peptide features. PointIso is the first point cloud based, arbitrary-precision deep learning network to address the problem and achieves 98% detection of high quality MS/MS identifications in a benchmark dataset, which is higher than several other widely used algorithms. Besides contributing to the proteomics study, we believe our novel segmentation technique should serve the general image processing domain as well.

Rui Qiao, Ngoc Hieu Tran, Lei Xin et al.

Personalized cancer vaccines are envisioned as the next generation rational cancer immunotherapy. The key step in developing personalized therapeutic cancer vaccines is to identify tumor-specific neoantigens that are on the surface of tumor cells. A promising method for this is through de novo peptide sequencing from mass spectrometry data. In this paper we introduce DeepNovoV2, the state-of-the-art model for peptide sequencing. In DeepNovoV2, a spectrum is directly represented as a set of (m/z, intensity) pairs, therefore it does not suffer from the accuracy-speed/memory trade-off problem. The model combines an order invariant network structure (T-Net) and recurrent neural networks and provides a complete end-to-end training and prediction framework to sequence patterns of peptides. Our experiments on a wide variety of data from different species show that DeepNovoV2 outperforms previous state-of-the-art methods, achieving 13.01-23.95\% higher accuracy at the peptide level.

Fatema Tuz Zohora, Ngoc Hieu Tran, Xianglilan Zhang et al.

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) based proteomics is a well-established research field with major applications such as identification of disease biomarkers, drug discovery, drug design and development. In proteomics, protein identification and quantification is a fundamental task, which is done by first enzymatically digesting it into peptides, and then analyzing peptides by LC-MS/MS instruments. The peptide feature detection and quantification from an LC-MS map is the first step in typical analysis workflows. In this paper we propose a novel deep learning based model, DeepIso, that uses Convolutional Neural Networks (CNNs) to scan an LC-MS map to detect peptide features and estimate their abundance. Existing tools are often designed with limited engineered features based on domain knowledge, and depend on pretrained parameters which are hardly updated despite huge amount of new coming proteomic data. Our proposed model, on the other hand, is capable of learning multiple levels of representation of high dimensional data through its many layers of neurons and continuously evolving with newly acquired data. To evaluate our proposed model, we use an antibody dataset including a heavy and a light chain, each digested by Asp-N, Chymotrypsin, Trypsin, thus giving six LC-MS maps for the experiment. Our model achieves 93.21% sensitivity with specificity of 99.44% on this dataset. Our results demonstrate that novel deep learning tools are desirable to advance the state-of-the-art in protein identification and quantification.