Disentangling the Complex Multiplexed DIA Spectra in De Novo Peptide Sequencing

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 system DeepNovo-DIA by from 25% to 81%, averaging 48%, for amino acid recall, and by from 27% to 89%, averaging 57%, for peptide recall, by 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.

C3D: Cascade Control with Change Point Detection and Deep Koopman Learning for Autonomous Surface Vehicles

In this paper, we discuss the development and deployment of a robust autonomous system capable of performing various tasks in the maritime domain under unknown dynamic conditions. We investigate a data-driven approach based on modular design for ease of transfer of autonomy across different maritime surface vessel platforms. The data-driven approach alleviates issues related to a priori identification of system models that may become deficient under evolving system behaviors or shifting, unanticipated, environmental influences. Our proposed learning-based platform comprises a deep Koopman system model and a change point detector that provides guidance on domain shifts prompting relearning under severe exogenous and endogenous perturbations. Motion control of the autonomous system is achieved via an optimal controller design. The Koopman linearized model naturally lends itself to a linear-quadratic regulator (LQR) control design. We propose the C3D control architecture Cascade Control with Change Point Detection and Deep Koopman Learning. The framework is verified in station keeping task on an ASV in both simulation and real experiments. The approach achieved at least 13.9 percent improvement in mean distance error in all test cases compared to the methods that do not consider system changes.

Modeling and Predicting Epidemic Spread: A Gaussian Process Regression Approach

Modeling and prediction of epidemic spread are critical to assist in policy-making for mitigation. Therefore, we present a new method based on Gaussian Process Regression to model and predict epidemics, and it quantifies prediction confidence through variance and high probability error bounds. Gaussian Process Regression excels in using small datasets and providing uncertainty bounds, and both of these properties are critical in modeling and predicting epidemic spreading processes with limited data. However, the derivation of formal uncertainty bounds remains lacking when using Gaussian Process Regression in the setting of epidemics, which limits its usefulness in guiding mitigation efforts. Therefore, in this work, we develop a novel bound on the variance of the prediction that quantifies the impact of the epidemic data on the predictions we make. Further, we develop a high probability error bound on the prediction, and we quantify how the epidemic spread, the infection data, and the length of the prediction horizon all affect this error bound. We also show that the error stays below a certain threshold based on the length of the prediction horizon. To illustrate this framework, we leverage Gaussian Process Regression to model and predict COVID-19 using real-world infection data from the United Kingdom.

Online Change Points Detection for Linear Dynamical Systems with Finite Sample Guarantees

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.

Learning Linearized Models from Nonlinear Systems with Finite Data

Identifying a linear system model from data has wide applications in control theory. The existing work on finite sample analysis for linear system identification typically uses data from a single 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. 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 demonstrates a trade-off between the error due to nonlinearity and the error due to noise, and shows that one can learn the linearized dynamics with arbitrarily small error given sufficiently many samples. We validate our results through 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.

Learning Dynamical Systems by Leveraging Data from Similar Systems

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 a finite sample error bound 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 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.

Finite Sample Guarantees for Distributed Online Parameter Estimation with Communication Costs

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.

Identifying the Dynamics of a System by Leveraging Data from Similar Systems

We study the problem of identifying the dynamics of a linear system when one has access to samples generated by a similar (but not identical) system, in addition to data from the true system. We use a weighted least squares approach and provide finite sample performance guarantees on the quality of the identified dynamics. Our results show that one can effectively use the auxiliary data generated by the similar system to reduce the estimation error due to the process noise, at the cost of adding a portion of error that is due to intrinsic differences in the models of the true and auxiliary systems. We also provide numerical experiments to validate our theoretical results. Our analysis can be applied to a variety of important settings. For example, if the system dynamics change at some point in time (e.g., due to a fault), how should one leverage data from the prior system in order to learn the dynamics of the new system? As another example, if there is abundant data available from a simulated (but imperfect) model of the true system, how should one weight that data compared to the real data from the system? Our analysis provides insights into the answers to these questions.

Learning the Dynamics of Autonomous Linear Systems From Multiple Trajectories

We consider the problem of learning the dynamics of autonomous linear systems (i.e., systems that are not affected by external control inputs) from observations of multiple trajectories of those systems, with finite sample guarantees. Existing results on learning rate and consistency of autonomous linear system identification rely on observations of steady state behaviors from a single long trajectory, and are not applicable to unstable systems. In contrast, we consider the scenario of learning system dynamics based on multiple short trajectories, where there are no easily observed steady state behaviors. We provide a finite sample analysis, which shows that the dynamics can be learned at a rate $\mathcal{O}(\frac{1}{\sqrt{N}})$ for both stable and unstable systems, where $N$ is the number of trajectories, when the initial state of the system has zero mean (which is a common assumption in the existing literature). We further generalize our result to the case where the initial state has non-zero mean. We show that one can adjust the length of the trajectories to achieve a learning rate of $\mathcal{O}(\sqrt{\frac{\log{N}}{N})}$ for strictly stable systems and a learning rate of $\mathcal{O}(\frac{(\log{N})^d}{\sqrt{N}})$ for marginally stable systems, where $d$ is some constant.

PointIso: Point Cloud Based Deep Learning Model for Detecting Arbitrary-Precision Peptide Features in LC-MS Map through Attention Based Segmentation

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.