Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development

PANINI : Pangenome Neighbour Identification for Bacterial Populations

The standard workhorse for genomic analysis of the evolution of bacterial populations is phylogenetic modelling of mutations in the core genome. However, a notable amount of information about evolutionary and transmission processes in diverse populations can be lost unless the accessory genome is also taken into consideration. Here, we introduce PANINI (Pangenome Neighbour Identification for Bacterial Populations), a computationally scalable method for identifying the neighbours for each isolate in a data set using unsupervised machine learning with stochastic neighbour embedding based on the t-SNE (t-distributed stochastic neighbour embedding) algorithm. PANINI is browser-based and integrates with the Microreact platform for rapid online visualization and exploration of both core and accessory genome evolutionary signals, together with relevant epidemiological, geographical, temporal and other metadata. Several case studies with single- and multi-clone pneumococcal populations are presented to demonstrate the ability to identify biologically important signals from gene content data. PANINI is available at http://panini.pathogen.watch and code at http://gitlab.com/cgps/panini.Peer reviewe

대용량 데이터 탐색을 위한 점진적 시각화 시스템 설계

학위논문(박사)--서울대학교 대학원 :공과대학 컴퓨터공학부,2020. 2. 서진욱.Understanding data through interactive visualization, also known as visual analytics, is a common and necessary practice in modern data science. However, as data sizes have increased at unprecedented rates, the computation latency of visualization systems becomes a significant hurdle to visual analytics. The goal of this dissertation is to design a series of systems for progressive visual analytics (PVA)—a visual analytics paradigm that can provide intermediate results during computation and allow visual exploration of these results—to address the scalability hurdle. To support the interactive exploration of data with billions of records, we first introduce SwiftTuna, an interactive visualization system with scalable visualization and computation components. Our performance benchmark demonstrates that it can handle data with four billion records, giving responsive feedback every few seconds without precomputation. Second, we present PANENE, a progressive algorithm for the Approximate k-Nearest Neighbor (AKNN) problem. PANENE brings useful machine learning methods into visual analytics, which has been challenging due to their long initial latency resulting from AKNN computation. In particular, we accelerate t-Distributed Stochastic Neighbor Embedding (t-SNE), a popular non-linear dimensionality reduction technique, which enables the responsive visualization of data with a few hundred columns. Each of these two contributions aims to address the scalability issues stemming from a large number of rows or columns in data, respectively. Third, from the users' perspective, we focus on improving the trustworthiness of intermediate knowledge gained from uncertain results in PVA. We propose a novel PVA concept, Progressive Visual Analytics with Safeguards, and introduce PVA-Guards, safeguards people can leave on uncertain intermediate knowledge that needs to be verified. We also present a proof-of-concept system, ProReveal, designed and developed to integrate seven safeguards into progressive data exploration. Our user study demonstrates that people not only successfully created PVA-Guards on ProReveal but also voluntarily used PVA-Guards to manage the uncertainty of their knowledge. Finally, summarizing the three studies, we discuss design challenges for progressive systems as well as future research agendas for PVA.현대 데이터 사이언스에서 인터랙티브한 시각화를 통해 데이터를 이해하는 것은 필수적인 분석 방법 중 하나이다. 그러나, 최근 데이터의 크기가 폭발적으로 증가하면서 데이터 크기로 인해 발생하는 지연 시간이 인터랙티브한 시각적 분석에 큰 걸림돌이 되었다. 본 연구에서는 이러한 확장성 문제를 해결하기 위해 점진적 시각적 분석(Progressive Visual Analytics)을 지원하는 일련의 시스템을 디자인하고 개발한다. 이러한 점진적 시각적 분석 시스템은 데이터 처리가 완전히 끝나지 않더라도 중간 분석 결과를 사용자에게 제공함으로써 데이터의 크기로 인해 발생하는 지연 시간 문제를 완화할 수 있다. 첫째로, 수십억 건의 행을 가지는 데이터를 시각적으로 탐색할 수 있는 SwiftTuna 시스템을 제안한다. 데이터 처리 및 시각적 표현의 확장성을 목표로 개발된 이 시스템은, 약 40억 건의 행을 가진 데이터에 대한 시각화를 전처리 없이 수 초마다 업데이트할 수 있는 것으로 나타났다. 둘째로, 근사적 k-최근접점(Approximate k-Nearest Neighbor) 문제를 점진적으로 계산하는 PANENE 알고리즘을 제안한다. 근사적 k-최근접점 문제는 여러 기계 학습 기법에서 쓰임에도 불구하고 초기 계산 시간이 길어서 인터랙티브한 시스템에 적용하기 힘든 한계가 있었다. PANENE 알고리즘은 이러한 긴 초기 계산 시간을 획기적으로 개선하여 다양한 기계 학습 기법을 시각적 분석에 활용할 수 있도록 한다. 특히, 유용한 비선형적 차원 감소 기법인 t-분포 확률적 임베딩(t-Distributed Stochastic Neighbor Embedding)을 가속하여 수백 개의 차원을 가지는 데이터를 빠른 시간 내에 사영할 수 있다. 위의 두 시스템과 알고리즘이 데이터의 행 또는 열의 개수로 인한 확장성 문제를 해결하고자 했다면, 세 번째 시스템에서는 점진적 시각적 분석의 신뢰도 문제를 개선하고자 한다. 점진적 시각적 분석에서 사용자에게 주어지는 중간 계산 결과는 최종 결과의 근사치이므로 불확실성이 존재한다. 본 연구에서는 세이프가드를 이용한 점진적 시각적 분석(Progressive Visual Analytics with Safeguards)이라는 새로운 개념을 제안한다. 이 개념은 사용자가 점진적 탐색에서 마주하는 불확실한 중간 지식에 세이프가드를 남길 수 있도록 하여 탐색에서 얻은 지식의 정확도를 추후 검증할 수 있도록 한다. 또한, 이러한 개념을 실제로 구현하여 탑재한 ProReveal 시스템을 소개한다. ProReveal를 이용한 사용자 실험에서 사용자들은 세이프가드를 성공적으로 만들 수 있었을 뿐만 아니라, 중간 지식의 불확실성을 다루기 위해 세이프가드를 자발적으로 이용한다는 것을 알 수 있었다. 마지막으로, 위 세 가지 연구의 결과를 종합하여 점진적 시각적 분석 시스템을 구현할 때의 디자인적 난제와 향후 연구 방향을 모색한다.CHAPTER1. Introduction 2 1.1 Background and Motivation 2 1.2 Thesis Statement and Research Questions 5 1.3 Thesis Contributions 5 1.3.1 Responsive and Incremental Visual Exploration of Large-scale Multidimensional Data 6 1.3.2 ProgressiveComputation of Approximate k-Nearest Neighbors and Responsive t-SNE 7 1.3.3 Progressive Visual Analytics with Safeguards 8 1.4 Structure of Dissertation 9 CHAPTER2. Related Work 11 2.1 Progressive Visual Analytics 11 2.1.1 Definitions 11 2.1.2 System Latency and Human Factors 13 2.1.3 Users, Tasks, and Models 15 2.1.4 Techniques, Algorithms, and Systems. 17 2.1.5 Uncertainty Visualization 19 2.2 Approaches for Scalable Visualization Systems 20 2.3 The k-Nearest Neighbor (KNN) Problem 22 2.4 t-Distributed Stochastic Neighbor Embedding 26 CHAPTER3. SwiTuna: Responsive and Incremental Visual Exploration of Large-scale Multidimensional Data 28 3.1 The SwiTuna Design 31 3.1.1 Design Considerations 32 3.1.2 System Overview 33 3.1.3 Scalable Visualization Components 36 3.1.4 Visualization Cards 40 3.1.5 User Interface and Interaction 42 3.2 Responsive Querying 44 3.2.1 Querying Pipeline 44 3.2.2 Prompt Responses 47 3.2.3 Incremental Processing 47 3.3 Evaluation: Performance Benchmark 49 3.3.1 Study Design 49 3.3.2 Results and Discussion 52 3.4 Implementation 56 3.5 Summary 56 CHAPTER4. PANENE:AProgressive Algorithm for IndexingandQuerying Approximate k-Nearest Neighbors 58 4.1 Approximate k-Nearest Neighbor 61 4.1.1 A Sequential Algorithm 62 4.1.2 An Online Algorithm 63 4.1.3 A Progressive Algorithm 66 4.1.4 Filtered AKNN Search 71 4.2 k-Nearest Neighbor Lookup Table 72 4.3 Benchmark. 78 4.3.1 Online and Progressive k-d Trees 78 4.3.2 k-Nearest Neighbor Lookup Tables 83 4.4 Applications 85 4.4.1 Progressive Regression and Density Estimation 85 4.4.2 Responsive t-SNE 87 4.5 Implementation 92 4.6 Discussion 92 4.7 Summary 93 CHAPTER5. ProReveal: Progressive Visual Analytics with Safeguards 95 5.1 Progressive Visual Analytics with Safeguards 98 5.1.1 Definition 98 5.1.2 Examples 101 5.1.3 Design Considerations 103 5.2 ProReveal 105 5.3 Evaluation 121 5.4 Discussion 127 5.5 Summary 130 CHAPTER6. Discussion 132 6.1 Lessons Learned 132 6.2 Limitations 135 CHAPTER7. Conclusion 137 7.1 Thesis Contributions Revisited 137 7.2 Future Research Agenda 139 7.3 Final Remarks 141 Abstract (Korean) 155 Acknowledgments (Korean) 157Docto

ROGUE:an R Shiny app for RNA sequencing analysis and biomarker discovery

Background: The growing power and ever decreasing cost of RNA sequencing (RNA-Seq) technologies have resulted in an explosion of RNA-Seq data production. Comparing gene expression values within RNA-Seq datasets is relatively easy for many interdisciplinary biomedical researchers; however, user-friendly software applications increase the ability of biologists to efficiently explore available datasets. Results: Here, we describe ROGUE (RNA-Seq Ontology Graphic User Environment, https://marisshiny.research.chop.edu/ROGUE/), a user-friendly R Shiny application that allows a biologist to perform differentially expressed gene analysis, gene ontology and pathway enrichment analysis, potential biomarker identification, and advanced statistical analyses. We use ROGUE to identify potential biomarkers and show unique enriched pathways between various immune cells. Conclusions: User-friendly tools for the analysis of next generation sequencing data, such as ROGUE, will allow biologists to efficiently explore their datasets, discover expression patterns, and advance their research by allowing them to develop and test hypotheses.</p