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Published work

34 published item(s)

preprint2026arXiv

Continuous Expert Assembly: Instance-Conditioned Low-Rank Residuals for All-in-One Image Restoration

Real-world image degradation is often unknown, spatially non-uniform, and compositional, requiring all-in-one restoration models to adapt a single set of weights to diverse local corruption patterns without test-time degradation labels. Existing methods typically modulate a shared backbone with global prompts or degradation descriptors, or route features through predefined expert pools. However, compact global conditioning can bottleneck localized degradation evidence, while static expert routing may produce homogeneous updates or rely on unstable sparse assignments. We propose \textbf{Continuous Expert Assembly} (CEA), a token-wise dynamic parameterization framework for all-in-one image restoration. CEA employs a lightweight \textbf{Cross-Attention Hyper-Adapter} to probe intermediate spatial features and synthesize instance-conditioned low-rank routing bases and residual directions. Each spatial token then assembles its own residual update via dense signed dot-product affinities over the generated rank-wise components, avoiding external prompts, static expert banks, and discrete Top- selection. The resulting assembly rule also admits a linear-attention perspective, making its dense token-wise routing behavior transparent. Experiments on AIO-3, AIO-5, and CDD-11 show that CEA improves average restoration quality over strong prompt-, descriptor-, and expert-based baselines, with the clearest gains on spatially varying and compositional degradations, while maintaining favorable parameter, FLOP, and runtime efficiency.

preprint2023arXiv

Studying Logging Practice in Machine Learning-based Applications

Logging is a common practice in traditional software development. Several research works have been done to investigate the different characteristics of logging practices in traditional software systems (e.g., Android applications, JAVA applications, C/C++ applications). Nowadays, we are witnessing more and more development of Machine Learning-based applications (ML-based applications). Today, there are many popular libraries that facilitate and contribute to the development of such applications, among which we can mention: Pytorch, Tensorflow, Theano, MXNet, Scikit-Learn, Caffe, and Keras. Despite the popularity of ML, we don't have a clear understanding of logging practices in ML applications. In this paper, we aim to fill this knowledge gap and help ML practitioners understand the characteristics of logging in ML-based applications. In particular, we conduct an empirical study on 110 open-source ML-based applications. Through a quantitative analysis, we find that logging practice in ML-based applications is less pervasive than in traditional applications including Android, JAVA, and C/C++ applications. Furthermore, the majority of logging statements in ML-based applications are in info and warn levels, compared to traditional applications where info is the majority of logging statement in C/C++ application and debug, error levels constitute the majority of logging statement in Android application. We also perform a quantitative and qualitative analysis of a random sample of logging statements to understand where ML developers put most of logging statements and examine why and how they are using logging. These analyses led to the following observations: (i) ML developers put most of the logging statements in model training, and in non-ML components. (ii) Data and model management appear to be the main reason behind the introduction of logging statements in ML-based applications.

preprint2022arXiv

A comparative study of non-deep learning, deep learning, and ensemble learning methods for sunspot number prediction

Solar activity has significant impacts on human activities and health. One most commonly used measure of solar activity is the sunspot number. This paper compares three important non-deep learning models, four popular deep learning models, and their five ensemble models in forecasting sunspot numbers. In particular, we propose an ensemble model called XGBoost-DL, which uses XGBoost as a two-level nonlinear ensemble method to combine the deep learning models. Our XGBoost-DL achieves the best forecasting performance (RMSE = 25.70 and MAE = 19.82) in the comparison, outperforming the best non-deep learning model SARIMA (RMSE = 54.11 and MAE = 45.51), the best deep learning model Informer (RMSE = 29.90 and MAE = 22.35) and the NASA's forecast (RMSE = 48.38 and MAE = 38.45). Our XGBoost-DL forecasts a peak sunspot number of 133.47 in May 2025 for Solar Cycle 25 and 164.62 in November 2035 for Solar Cycle 26, similar to but later than the NASA's at 137.7 in October 2024 and 161.2 in December 2034. An open-source Python package of our XGBoost-DL for the sunspot number prediction is available at https://github.com/yd1008/ts_ensemble_sunspot.

preprint2022arXiv

An Empirical Study on the Usage of Automated Machine Learning Tools

The popularity of automated machine learning (AutoML) tools in different domains has increased over the past few years. Machine learning (ML) practitioners use AutoML tools to automate and optimize the process of feature engineering, model training, and hyperparameter optimization and so on. Recent work performed qualitative studies on practitioners' experiences of using AutoML tools and compared different AutoML tools based on their performance and provided features, but none of the existing work studied the practices of using AutoML tools in real-world projects at a large scale. Therefore, we conducted an empirical study to understand how ML practitioners use AutoML tools in their projects. To this end, we examined the top 10 most used AutoML tools and their respective usages in a large number of open-source project repositories hosted on GitHub. The results of our study show 1) which AutoML tools are mostly used by ML practitioners and 2) the characteristics of the repositories that use these AutoML tools. Also, we identified the purpose of using AutoML tools (e.g. model parameter sampling, search space management, model evaluation/error-analysis, Data/ feature transformation, and data labeling) and the stages of the ML pipeline (e.g. feature engineering) where AutoML tools are used. Finally, we report how often AutoML tools are used together in the same source code files. We hope our results can help ML practitioners learn about different AutoML tools and their usages, so that they can pick the right tool for their purposes. Besides, AutoML tool developers can benefit from our findings to gain insight into the usages of their tools and improve their tools to better fit the users' usages and needs.

preprint2022arXiv

Bug Characteristics in Quantum Software Ecosystem

With the advance in quantum computing in recent years, quantum software becomes vital for exploring the full potential of quantum computing systems. Quantum programming is different from classical programming, for example, the state of a quantum program is probabilistic in nature, and a quantum computer is error-prone due to the instability of quantum mechanisms. Therefore, the characteristics of bugs in quantum software projects may be very different from that of classical software projects. This work aims to understand the characteristics of bugs in quantum software projects, in order to provide insights to help devise effective testing and debugging mechanisms. To achieve this goal, we conduct an empirical study on the bug reports of 125 quantum software projects. We observe that quantum software projects are more buggy than classical software projects and that quantum project bugs are more costly to fix than classical project bugs. We also identify the types of the bugs and the quantum programming components where they occurred. Our study shows that the bugs are spread across different components, but quantum-specific bugs particularly appear in the compiler, gate operation, and state preparation components. The three most occurring types of bugs are Program anomaly bugs, Configuration bugs, and Data type and structure bugs. Our study highlights some particularly challenging areas in quantum software development, such as the lack of scientific quantum computation libraries that implement comprehensive mathematical functions for quantum computing. Quantum developers also seek specialized data manipulation libraries for quantum software engineering like Numpy for quantum computing. Our findings also provide insights for future work to advance the quantum program development, testing, and debugging of quantum software, such as providing tooling support for debugging low-level circuits.

preprint2022arXiv

Fast sequence to graph alignment using the graph wavefront algorithm

Motivation: A pan-genome graph represents a collection of genomes and encodes sequence variations between them. It is a powerful data structure for studying multiple similar genomes. Sequence-to-graph alignment is an essential step for the construction and the analysis of pan-genome graphs. However, existing algorithms incur runtime proportional to the product of sequence length and graph size, making them inefficient for aligning long sequences against large graphs. Results: We propose the graph wavefront alignment algorithm (Gwfa), a new method for aligning a sequence to a sequence graph. Although the worst-case time complexity of Gwfa is the same as the existing algorithms, it is designed to run faster for closely matching sequences, and its runtime in practice often increases only moderately with the edit distance of the optimal alignment. On four real datasets, Gwfa is up to four orders of magnitude faster than other exact sequence-to-graph alignment algorithms. We also propose a graph pruning heuristic on top of Gwfa, which can achieve an additional $\sim$10-fold speedup on large graphs. Availability: Gwfa code is accessible at https://github.com/lh3/gwfa.

preprint2022arXiv

FB-MSTCN: A Full-Band Single-Channel Speech Enhancement Method Based on Multi-Scale Temporal Convolutional Network

In recent years, deep learning-based approaches have significantly improved the performance of single-channel speech enhancement. However, due to the limitation of training data and computational complexity, real-time enhancement of full-band (48 kHz) speech signals is still very challenging. Because of the low energy of spectral information in the high-frequency part, it is more difficult to directly model and enhance the full-band spectrum using neural networks. To solve this problem, this paper proposes a two-stage real-time speech enhancement model with extraction-interpolation mechanism for a full-band signal. The 48 kHz full-band time-domain signal is divided into three sub-channels by extracting, and a two-stage processing scheme of `masking + compensation' is proposed to enhance the signal in the complex domain. After the two-stage enhancement, the enhanced full-band speech signal is restored by interval interpolation. In the subjective listening and word accuracy test, our proposed model achieves superior performance and outperforms the baseline model overall by 0.59 MOS and 4.0% WAcc for the non-personalized speech denoising task.

preprint2022arXiv

Generating non-jumps from a known one

Let $r\ge 2$ be an integer. The real number $α\in [0,1]$ is a jump for $r$ if there exists a constant $c > 0$ such that for any $ε>0$ and any integer $m \geq r$, there exists an integer $n_0(ε, m)$ satisfying any $r$-uniform graph with $n\ge n_0(ε, m)$ vertices and density at least $α+ε$ contains a subgraph with $m$ vertices and density at least $α+c$. A result of Erdős, Stone and Simonovits implies that every $α\in [0,1)$ is a jump for $r=2$. Erdős asked whether the same is true for $r\ge 3$. Frankl and Rödl gave a negative answer by showing that $1-\frac{1}{l^{r-1}}$ is not a jump for $r$ if $r\ge 3$ and $l>2r$. After that, more non-jumps are found using a method of Frankl and Rödl. In this note, we show a method to construct maps $f \colon [0,1] \to [0,1]$ that preserve non-jumps, if $α$ is a non-jump for $r$ given by the method of Frankl and Rödl, then $f(α)$ is also a non-jump for $r$. We use these maps to study hypergraph Turán densities and answer a question posed by Grosu.

preprint2022arXiv

Intrinsic spin-momentum dynamics of surface electromagnetic waves in complex dispersive system

Spin-momentum locking is an intrinsic property of surface electromagnetic fields and its study has led to the discovery of photonic spin lattices and diverse applications. Previously, dispersion was ignored in the spin-momentum locking, giving rise to abnormal phenomena contradictory to the physical realities. Here, we formulate four dispersive spin-momentum equations for surface waves, revealing universally that the transverse spin vector is locked with the momentum. The locking property obeys the right-hand rule in the dielectric but the left-hand rule in the dispersive metal/magnetic materials. In addition to the dispersion, the structural features can affect the spin-momentum locking significantly. Remarkably, an extraordinary longitudinal spin originating from the coupling polarization ellipticity is uncovered even for the purely polarized state. We further demonstrate the spin-momentum locking properties with diverse photonic topological lattices by engineering the rotating symmetry. The findings open up opportunities for designing robust nanodevices with practical importance in chiral quantum optics.

preprint2022arXiv

On the Importance of Performing App Analysis Within Peer Groups

The competing nature of the app market motivates us to shift our focus on apps that provide similar functionalities and directly compete with each other (i.e., peer apps). In this work, we study the ratings and the review text of 100 Android apps across 10 peer app groups. We highlight the importance of performing peer-app analysis by showing that it can provide a unique perspective over performing a global analysis of apps (i.e., mixing apps from multiple categories). First, we observe that comparing user ratings within peer groups can provide very different results from comparing user ratings from a global perspective. Then, we show that peer-app analysis provides a different perspective to spot the dominant topics in the user reviews, and to understand the impact of the topics on user ratings. Our findings suggest that future efforts may pay more attention to performing and supporting app analysis from a peer group context. For example, app store owners may consider an additional rating mechanism that normalizes app ratings within peer groups, and future research may help developers understand the characteristics of specific peer groups and prioritize their efforts.

preprint2022arXiv

Singularity-Avoidance Prescribed Performance Attitude Tracking of Spacecraft

The attitude tracking problem with preassigned performance requirements has earned tremendous interest in recent years, and the Prescribed Performance Control (PPC) scheme is often adopted to tackle this problem. Nevertheless, traditional PPC schemes have inherent problems, which the solution still lacks, such as the singularity problem when the state constraint is violated and the potential over-control problem when the state trajectory approaches the constraint boundary. This paper proposes a Singularity-Avoidance Prescribed Performance Control scheme (SAPPC) to deal with these problems. A novel shear mapping-based error transformation is proposed to provide a globally non-singular error transformation procedure, while a time-varying constraint boundary is employed to exert appropriate constraint strength at different control stages, alleviating the potential instability caused by the over-control problem. Besides, a novel piece-wise reference performance function (RPF) is constructed to provide a relevant reference trajectory for the state responding signals, allowing precise control of the system's responding behavior. Based on the proposed SAPPC scheme, a backstepping controller is developed, with the predefined-time stability technique and the dynamic surface control technique employed to enhance the controller's robustness and performance. Finally, theoretical analysis and numerical simulation results are presented to validate the proposed control scheme's effectiveness and robustness.

preprint2022arXiv

SOFFLFM: Super-resolution optical fluctuation Fourier light-field microscopy

Fourier light-field microscopy (FLFM) uses a micro-lens array (MLA) to segment the Fourier Plane of the microscopic objective lens to generate multiple two-dimensional perspective views, thereby reconstructing the three-dimensional(3D) structure of the sample using 3D deconvolution calculation without scanning. However, the resolution of FLFM is still limited by diffraction, and furthermore, dependent on the aperture division. In order to improve its resolution, a Super-resolution optical fluctuation Fourier light field microscopy (SOFFLFM) was proposed here, in which the Sofi method with ability of super-resolution was introduced into FLFM. SOFFLFM uses higher-order cumulants statistical analysis on an image sequence collected by FLFM, and then carries out 3D deconvolution calculation to reconstruct the 3D structure of the sample. Theoretical basis of SOFFLFM on improving resolution was explained and then verified with simulations. Simulation results demonstrated that SOFFLFM improved lateral and axial resolution by more than sqrt(2) and 2 times in the 2nd and 4th order accumulations, compared with that of FLFM.

preprint2022arXiv

Spacecraft Attitude Pointing Control under Pointing Forbidden Constraints with Guaranteed Accuracy

This paper focuses on the attitude pointing control problem under pointing-forbidden constraints and performance constraints. The spacecraft is expected to align its sensor's boresight to a desired direction, while the terminal control accuracy and the attitude adjustment rapidity should also be guaranteed simultaneously. To resolve this problem, a switching controller structure is proposed in this paper based on the reduced-attitude representation, fusing the artificial potential field (APF) methodology and the Prescribed Performance Control (PPC) scheme together. Firstly, a novel artificial potential field is presented, and a particular function is designed for the mollification of the switching process, aiming at providing a smooth transition for the system status. Subsequently, we propose a special performance function, which can freeze the PPC part when necessary. In this way, the intrinsic contradictory between the fast attitude maneuver and forbidden direction avoidance is tackled Further, an asynchronous switching strategy is designed, guarantees the system's stability. Based on these proposed issues, a switching backstepping controller is developed, and a tracking differentiator(TD) is employed to generate a smooth approximation of differential signals. Numerical simulation results are illustrated to show the effectiveness of the proposed scheme.

preprint2022arXiv

Structure-consistent Restoration Network for Cataract Fundus Image Enhancement

Fundus photography is a routine examination in clinics to diagnose and monitor ocular diseases. However, for cataract patients, the fundus image always suffers quality degradation caused by the clouding lens. The degradation prevents reliable diagnosis by ophthalmologists or computer-aided systems. To improve the certainty in clinical diagnosis, restoration algorithms have been proposed to enhance the quality of fundus images. Unfortunately, challenges remain in the deployment of these algorithms, such as collecting sufficient training data and preserving retinal structures. In this paper, to circumvent the strict deployment requirement, a structure-consistent restoration network (SCR-Net) for cataract fundus images is developed from synthesized data that shares an identical structure. A cataract simulation model is firstly designed to collect synthesized cataract sets (SCS) formed by cataract fundus images sharing identical structures. Then high-frequency components (HFCs) are extracted from the SCS to constrain structure consistency such that the structure preservation in SCR-Net is enforced. The experiments demonstrate the effectiveness of SCR-Net in the comparison with state-of-the-art methods and the follow-up clinical applications. The code is available at https://github.com/liamheng/ArcNet-Medical-Image-Enhancement.

preprint2022arXiv

Studying the Practices of Deploying Machine Learning Projects on Docker

Docker is a containerization service that allows for convenient deployment of websites, databases, applications' APIs, and machine learning (ML) models with a few lines of code. Studies have recently explored the use of Docker for deploying general software projects with no specific focus on how Docker is used to deploy ML-based projects. In this study, we conducted an exploratory study to understand how Docker is being used to deploy ML-based projects. As the initial step, we examined the categories of ML-based projects that use Docker. We then examined why and how these projects use Docker, and the characteristics of the resulting Docker images. Our results indicate that six categories of ML-based projects use Docker for deployment, including ML Applications, MLOps/ AIOps, Toolkits, DL Frameworks, Models, and Documentation. We derived the taxonomy of 21 major categories representing the purposes of using Docker, including those specific to models such as model management tasks (e.g., testing, training). We then showed that ML engineers use Docker images mostly to help with the platform portability, such as transferring the software across the operating systems, runtimes such as GPU, and language constraints. However, we also found that more resources may be required to run the Docker images for building ML-based software projects due to the large number of files contained in the image layers with deeply nested directories. We hope to shed light on the emerging practices of deploying ML software projects using containers and highlight aspects that should be improved.

preprint2022arXiv

Understanding Quantum Software Engineering Challenges An Empirical Study on Stack Exchange Forums and GitHub Issues

With the advance in quantum computing, quantum software becomes critical for exploring the full potential of quantum computing systems. Recently, quantum software engineering (QSE) becomes an emerging area attracting more and more attention. However, it is not clear what are the challenges and opportunities of quantum computing facing the software engineering community. This work aims to understand the QSE-related challenges perceived by developers. We perform an empirical study on Stack Exchange forums where developers post-QSE-related questions & answers and Github issue reports where developers raise QSE-related issues in practical quantum computing projects. Based on an existing taxonomy of question types on Stack Overflow, we first perform a qualitative analysis of the types of QSE-related questions asked on Stack Exchange forums. We then use automated topic modeling to uncover the topics in QSE-related Stack Exchange posts and GitHub issue reports. Our study highlights some particularly challenging areas of QSE that are different from that of traditional software engineering, such as explaining the theory behind quantum computing code, interpreting quantum program outputs, and bridging the knowledge gap between quantum computing and classical computing, as well as their associated opportunities.

preprint2021arXiv

Constructing Sub-scale Surrogate Model for Proppant Settling in Inclined Fractures from Simulation Data with Multi-fidelity Neural Network

Particle settling in inclined channels is an important phenomenon that occurs during hydraulic fracturing of shale gas production. Generally, in order to accurately simulate the large-scale (field-scale) proppant transport process, constructing a fast and accurate sub-scale proppant settling model, or surrogate model, becomes a critical issue, since mapping between physical parameters and proppant settling velocity is complex. Previously, particle settling has usually been investigated via high-fidelity experiments and meso-scale numerical simulations, both of which are time-consuming. In this work, a new method is proposed and utilized, i.e., the multi-fidelity neural network (MFNN), to construct a settling surrogate model, which could utilize both high-fidelity and low-fidelity (thus, less expensive) data. The results demonstrate that constructing the settling surrogate with the MFNN can reduce the need for high-fidelity data and thus computational cost by 80%, while the accuracy lost is less than 5% compared to a high-fidelity surrogate. Moreover, the investigated particle settling surrogate is applied in macro-scale proppant transport simulation, which shows that the settling model is significant to proppant transport and yields accurate results. This opens novel pathways for rapidly predicting proppant settling velocity in reservoir applications.

preprint2021arXiv

Twelve years of SAMtools and BCFtools

Background SAMtools and BCFtools are widely used programs for processing and analysing high-throughput sequencing data. Findings The first version appeared online twelve years ago and has been maintained and further developed ever since, with many new features and improvements added over the years. The SAMtools and BCFtools packages represent a unique collection of tools that have been used in numerous other software projects and countless genomic pipelines. Conclusion Both SAMtools and BCFtools are freely available on GitHub under the permissive MIT licence, free for both non-commercial and commercial use. Both packages have been installed over a million times via Bioconda. The source code and documentation are available from http://www.htslib.org.

preprint2020arXiv

BGM: Building a Dynamic Guidance Map without Visual Images for Trajectory Prediction

Visual images usually contain the informative context of the environment, thereby helping to predict agents' behaviors. However, they hardly impose the dynamic effects on agents' actual behaviors due to the respectively fixed semantics. To solve this problem, we propose a deterministic model named BGM to construct a guidance map to represent the dynamic semantics, which circumvents to use visual images for each agent to reflect the difference of activities in different periods. We first record all agents' activities in the scene within a period close to the current to construct a guidance map and then feed it to a Context CNN to obtain their context features. We adopt a Historical Trajectory Encoder to extract the trajectory features and then combine them with the context feature as the input of the social energy based trajectory decoder, thus obtaining the prediction that meets the social rules. Experiments demonstrate that BGM achieves state-of-the-art prediction accuracy on the two widely used ETH and UCY datasets and handles more complex scenarios.

preprint2020arXiv

Haplotype-resolved de novo assembly with phased assembly graphs

Haplotype-resolved de novo assembly is the ultimate solution to the study of sequence variations in a genome. However, existing algorithms either collapse heterozygous alleles into one consensus copy or fail to cleanly separate the haplotypes to produce high-quality phased assemblies. Here we describe hifiasm, a new de novo assembler that takes advantage of long high-fidelity sequence reads to faithfully represent the haplotype information in a phased assembly graph. Unlike other graph-based assemblers that only aim to maintain the contiguity of one haplotype, hifiasm strives to preserve the contiguity of all haplotypes. This feature enables the development of a graph trio binning algorithm that greatly advances over standard trio binning. On three human and five non-human datasets, including California redwood with a $\sim$30-gigabase hexaploid genome, we show that hifiasm frequently delivers better assemblies than existing tools and consistently outperforms others on haplotype-resolved assembly.

preprint2020arXiv

Logram: Efficient Log Parsing Using n-Gram Dictionaries

Software systems usually record important runtime information in their logs. Logs help practitioners understand system runtime behaviors and diagnose field failures. As logs are usually very large in size, automated log analysis is needed to assist practitioners in their software operation and maintenance efforts. Typically, the first step of automated log analysis is log parsing, i.e., converting unstructured raw logs into structured data. However, log parsing is challenging, because logs are produced by static templates in the source code (i.e., logging statements) yet the templates are usually inaccessible when parsing logs. Prior work proposed automated log parsing approaches that have achieved high accuracy. However, as the volume of logs grows rapidly in the era of cloud computing, efficiency becomes a major concern in log parsing. In this work, we propose an automated log parsing approach, Logram, which leverages n-gram dictionaries to achieve efficient log parsing. We evaluated Logram on 16 public log datasets and compared Logram with five state-of-the-art log parsing approaches. We found that Logram achieves a similar parsing accuracy to the best existing approaches while outperforms these approaches in efficiency (i.e., 1.8 to 5.1 times faster than the second fastest approaches). Furthermore, we deployed Logram on Spark and we found that Logram scales out efficiently with the number of Spark nodes (e.g., with near-linear scalability) without sacrificing parsing accuracy. In addition, we demonstrated that Logram can support effective online parsing of logs, achieving similar parsing results and efficiency with the offline mode.

preprint2020arXiv

The design and construction of reference pangenome graphs

The recent advances in sequencing technologies enables the assembly of individual genomes to the reference quality. How to integrate multiple genomes from the same species and to make the integrated representation accessible to biologists remain an open challenge. Here we propose a graph-based data model and associated formats to represent multiple genomes while preserving the coordinate of the linear reference genome. We implemented our ideas in the minigraph toolkit and demonstrate that we can efficiently construct a pangenome graph and compactly encode tens of thousands of structural variants missing from the current reference genome.

preprint2019arXiv

Deep Learning of Subsurface Flow via Theory-guided Neural Network

Active researches are currently being performed to incorporate the wealth of scientific knowledge into data-driven approaches (e.g., neural networks) in order to improve the latter's effectiveness. In this study, the Theory-guided Neural Network (TgNN) is proposed for deep learning of subsurface flow. In the TgNN, as supervised learning, the neural network is trained with available observations or simulation data while being simultaneously guided by theory (e.g., governing equations, other physical constraints, engineering controls, and expert knowledge) of the underlying problem. The TgNN can achieve higher accuracy than the ordinary Artificial Neural Network (ANN) because the former provides physically feasible predictions and can be more readily generalized beyond the regimes covered with the training data. Furthermore, the TgNN model is proposed for subsurface flow with heterogeneous model parameters. Several numerical cases of two-dimensional transient saturated flow are introduced to test the performance of the TgNN. In the learning process, the loss function contains data mismatch, as well as PDE constraint, engineering control, and expert knowledge. After obtaining the parameters of the neural network by minimizing the loss function, a TgNN model is built that not only fits the data, but also adheres to physical/engineering constraints. Predicting the future response can be easily realized by the TgNN model. In addition, the TgNN model is tested in more complicated scenarios, such as prediction with changed boundary conditions, learning from noisy data or outliers, transfer learning, and engineering controls. Numerical results demonstrate that the TgNN model achieves much better predictability, reliability, and generalizability than ANN models due to the physical/engineering constraints in the former.

preprint2015arXiv

Correcting Illumina sequencing errors for human data

Summary: We present a new tool to correct sequencing errors in Illumina data produced from high-coverage whole-genome shotgun resequencing. It uses a non-greedy algorithm and shows comparable performance and higher accuracy in an evaluation on real human data. This evaluation has the most complete collection of high-performance error correctors so far. Availability and implementation: https://github.com/lh3/bfc Contact: hengli@broadinstitute.org

preprint2015arXiv

FermiKit: assembly-based variant calling for Illumina resequencing data

Summary: FermiKit is a variant calling pipeline for Illumina data. It de novo assembles short reads and then maps the assembly against a reference genome to call SNPs, short insertions/deletions (INDELs) and structural variations (SVs). FermiKit takes about one day to assemble 30-fold human whole-genome data on a modern 16-core server with 85GB RAM at the peak, and calls variants in half an hour to an accuracy comparable to the current practice. FermiKit assembly is a reduced representation of raw data while retaining most of the original information. Availability and implementation: https://github.com/lh3/fermikit Contact: hengli@broadinstitute.org

preprint2014arXiv

Ancient human genomes suggest three ancestral populations for present-day Europeans

We sequenced genomes from a $\sim$7,000 year old early farmer from Stuttgart in Germany, an $\sim$8,000 year old hunter-gatherer from Luxembourg, and seven $\sim$8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations' deep relationships and show that EEF had $\sim$44% ancestry from a "Basal Eurasian" lineage that split prior to the diversification of all other non-African lineages.

preprint2014arXiv

Fast construction of FM-index for long sequence reads

Summary: We present a new method to incrementally construct the FM-index for both short and long sequence reads, up to the size of a genome. It is the first algorithm that can build the index while implicitly sorting the sequences in the reverse (complement) lexicographical order without a separate sorting step. The implementation is among the fastest for indexing short reads and the only one that practically works for reads of averaged kilobases in length. Availability and implementation: https://github.com/lh3/ropebwt2 Contact: hengli@broadinstitute.org

preprint2014arXiv

No evidence that natural selection has been less effective at removing deleterious mutations in Europeans than in West Africans

Non-African populations have experienced major bottlenecks in the time since their split from West Africans, which has led to the hypothesis that natural selection to remove weakly deleterious mutations may have been less effective in non-Africans. To directly test this hypothesis, we measure the per-genome accumulation of deleterious mutations across diverse humans. We fail to detect any significant differences, but find that archaic Denisovans accumulated non-synonymous mutations at a higher rate than modern humans, consistent with the longer separation time of modern and archaic humans. We also revisit the empirical patterns that have been interpreted as evidence for less effective removal of deleterious mutations in non-Africans than in West Africans, and show they are not driven by differences in selection after population separation, but by neutral evolution.

preprint2013arXiv

A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data

Motivation: Most existing methods for DNA sequence analysis rely on accurate sequences or genotypes. However, in applications of the next-generation sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi-sample low-coverage sequencing or somatic mutation discovery). These applications press for the development of new methods for analyzing sequence data with uncertainty. Results: We present a statistical framework for calling SNPs, discovering somatic mutations, inferring population genetical parameters and performing association tests directly based on sequencing data without explicit genotyping or linkage-based imputation. On real data, we demonstrate that our method achieves comparable accuracy to alternative methods for estimating site allele count, for inferring allele frequency spectrum and for association mapping. We also highlight the necessity of using symmetric datasets for finding somatic mutations and confirm that for discovering rare events, mismapping is frequently the leading source of errors. Availability: http://samtools.sourceforge.net. Contact: hengli@broadinstitute.org.

preprint2013arXiv

Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM

Summary: BWA-MEM is a new alignment algorithm for aligning sequence reads or long query sequences against a large reference genome such as human. It automatically chooses between local and end-to-end alignments, supports paired-end reads and performs chimeric alignment. The algorithm is robust to sequencing errors and applicable to a wide range of sequence lengths from 70bp to a few megabases. For mapping 100bp sequences, BWA-MEM shows better performance than several state-of-art read aligners to date. Availability and implementation: BWA-MEM is implemented as a component of BWA, which is available at http://github.com/lh3/bwa. Contact: hengli@broadinstitute.org

preprint2013arXiv

Demonstration of Low Emittance in the Cornell Energy Recovery Linac Injector Prototype

We present a detailed study of the six-dimensional phase space of the electron beam produced by the Cornell Energy Recovery Linac Photoinjector, a high-brightness, high repetition rate (1.3 GHz) DC photoemission source designed to drive a hard x-ray energy recovery linac (ERL). A complete simulation model of the injector has been constructed, verified by measurement, and optimized. Both the horizontal and vertical 2D transverse phase spaces, as well as the time-resolved (sliced) horizontal phase space, were simulated and directly measured at the end of the injector for 19 pC and 77 pC bunches at roughly 8 MeV. These bunch charges were chosen because they correspond to 25 mA and 100 mA average current if operating at the full 1.3 GHz repetition rate. The resulting 90% normalized transverse emittances for 19 (77) pC/bunch were 0.23 +/- 0.02 (0.51 +/- 0.04) microns in the horizontal plane, and 0.14 +/- 0.01 (0.29 +/- 0.02) microns in the vertical plane, respectively. These emittances were measured with a corresponding bunch length of 2.1 +/- 0.1 (3.0 +/- 0.2) ps, respectively. In each case the rms momentum spread was determined to be on the order of 1e-3. Excellent overall agreement between measurement and simulation has been demonstrated. Using the emittances and bunch length measured at 19 pC/bunch, we estimate the electron beam quality in a 1.3 GHz, 5 GeV hard x-ray ERL to be at least a factor of 20 times better than that of existing storage rings when the rms energy spread of each device is considered. These results represent a milestone for the field of high-brightness, high-current photoinjectors.

preprint2012arXiv

Exploring single-sample SNP and INDEL calling with whole-genome de novo assembly

Motivation: Eugene Myers in his string graph paper (Myers, 2005) suggested that in a string graph or equivalently a unitig graph, any path spells a valid assembly. As a string/unitig graph also encodes every valid assembly of reads, such a graph, provided that it can be constructed correctly, is in fact a lossless representation of reads. In principle, every analysis based on whole-genome shotgun sequencing (WGS) data, such as SNP and insertion/deletion (INDEL) calling, can also be achieved with unitigs. Results: To explore the feasibility of using de novo assembly in the context of resequencing, we developed a de novo assembler, fermi, that assembles Illumina short reads into unitigs while preserving most of information of the input reads. SNPs and INDELs can be called by mapping the unitigs against a reference genome. By applying the method on 35-fold human resequencing data, we showed that in comparison to the standard pipeline, our approach yields similar accuracy for SNP calling and better results for INDEL calling. It has higher sensitivity than other de novo assembly based methods for variant calling. Our work suggests that variant calling with de novo assembly be a beneficial complement to the standard variant calling pipeline for whole-genome resequencing. In the methodological aspects, we proposed FMD-index for forward-backward extension of DNA sequences, a fast algorithm for finding all super-maximal exact matches and one-pass construction of unitigs from an FMD-index. Availability: http://github.com/lh3/fermi Contact: hengli@broadinstitute.org

preprint2012arXiv

The date of interbreeding between Neandertals and modern humans

Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000-65,000 years ago. This supports the recent interbreeding hypothesis, and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.

preprint2011arXiv

Creating and modulating electronic states on noble metal surfaces: ultrathin Ag islands on Si(111)-7$\times$7 as a prototype

Various-thickness Ag islands were prepared on Si(111)-7$\times$7 using the one-step deposition at a high substrate temperature. An electronic state centered at -0.40$\sim$-0.15eV versus E$_{Fermi}$, detectable on the surface of the Ag islands thinner than 9 layers, was created by the electronic hybridization between Ag and Si at the Ag-Si interface. Scanning tunneling microscopy/spectroscopy and density functional theory revealed that the thickness of Ag islands determined the strength of the hybridization, leading to a modulation to the energy and intensity of the state on the surface.