Cluster Tool Research Articles

Well-connectedness and community detection

Community detection methods help reveal the meso-scale structure of complex networks. Integral to detecting communities is the expectation that communities in a network are edge-dense and “well-connected”. Surprisingly, we find that five different community detection methods–the Leiden algorithm optimizing the Constant Potts Model, the Leiden algorithm optimizing modularity, Infomap, Markov Cluster (MCL), and Iterative k-core (IKC)–identify communities that fail even a mild requirement for well-connectedness. To address this issue, we have developed the Connectivity Modifier (CM), which iteratively removes small edge cuts and re-clusters until communities are well-connected according to a user-specified criterion. We tested CM on real-world networks ranging in size from approximately 35,000 to 75,000,000 nodes. Post-processing of the output of community detection methods by CM resulted in a reduction in node coverage. Results on synthetic networks show that the CM algorithm generally maintains or improves accuracy in recovering true communities. This study underscores the importance of network clusterability–the fraction of a network that exhibits community structure–and the need for more models of community structure where networks contain nodes that are not assigned to communities. In summary, we address well-connectedness as an important aspect of clustering and present a scalable open-source tool for well-connected clusters.

A Clustering Approach to Unveil User Similarities in 6-DoF Extended Reality Applications

The advent in our daily life of Extended Reality (XR) technologies, such as Virtual and Augmented Reality, has led to the rise of user-centric systems, offering higher level of interaction and presence in virtual environments. In this context, understanding the actual interactivity of users is still an open challenge and a key step to enabling user-centric system. In this work, our goal is to construct an efficient clustering tool for 6 Degree-of-Freedom (DoF) navigation trajectories by extending the applicability of existing behavioural tool. Specifically, we first compare the navigation in 6-DoF with its 3-DoF counterpart, highlighting the main differences and novelties. Then, we investigate new metrics aimed at better modelling behavioural similarities between users in a 6-DoF system. More concretely, we define and compare 11 similarity metrics which are based on different distance features ( i.e. , user positions in the 3D space, user viewing directions) and distance measurements ( i.e. , Euclidean, Geodesic, angular distance). Our solutions are validated and tested on real navigation paths of users interacting with dynamic volumetric media in both 6-DoF Virtual Reality and Augmented Reality conditions. Results show that metrics based on both user position and viewing direction better perform in detecting user similarity while navigating in a 6-DoF system. Such easy-to-use but robust metrics allow us to answer a fundamental question for user-centric systems: “how do we detect if users look at the same content in 6-DoF?”, opening the gate to new solutions based on users interactivity, such as viewport prediction, live streaming services optimised based on users behaviour but also for user-based quality assessment methods.

Computational algorithm based on health and lifestyle traits to categorize lifemetabotypes in the NUTRiMDEA cohort

Classifying individuals based on metabotypes and lifestyle phenotypes using exploratory factor analyses, cluster definition, and machine-learning algorithms is promising for precision chronic disease prevention and management. This study analyzed data from the NUTRiMDEA online cohort (baseline: n = 17332 and 62 questions) to develop a clustering tool based on 32 accessible questions using machine-learning strategies. Participants ranged from 18 to over 70 years old, with 64.1% female and 35.5% male. Five clusters were identified, combining metabolic, lifestyle, and personal data: Cluster 1 (“Westernized Millennial”, n = 967) included healthy young individuals with fair lifestyle habits; Cluster 2 (“Healthy”, n = 10616) consisted of healthy adults; Cluster 3 (“Mediterranean Young Adult”, n = 2013) represented healthy young adults with a healthy lifestyle and showed the highest adherence to the Mediterranean diet; Cluster 4 (“Pre-morbid”, n = 600) was characterized by healthy adults with declined mood; Cluster 5 (“Pro-morbid”, n = 312) comprised older individuals (47% >55 years) with poorer lifestyle habits, worse health, and a lower health-related quality of life. A computational algorithm was elicited, which allowed quick cluster assignment based on responses (“lifemetabotypes”). This machine-learning approach facilitates personalized interventions and precision lifestyle recommendations, supporting online methods for targeted health maintenance and chronic disease prevention.

Inferring ancestry with the hierarchical soft clustering approach tangleGen.

Understanding the genetic ancestry of populations is central to numerous scientific and societal fields. It contributes to a better understanding of human evolutionary history, advances personalized medicine, aids in forensic identification, and allows individuals to connect to their genealogical roots. Existing methods, such as ADMIXTURE, have significantly improved our ability to infer ancestries. However, these methods typically work with a fixed number of independent ancestral populations. As a result, they provide insight into genetic admixture, but do not include a hierarchical interpretation. In particular, the intricate ancestral population structures remain difficult to unravel. Alternative methods with a consistent inheritance structure, such as hierarchical clustering, may offer benefits in terms of interpreting the inferred ancestries. Here, we present tangleGen, a soft clustering tool that transfers the hierarchical machine learning framework Tangles, which leverages graph theoretical concepts, to the field of population genetics. The hierarchical perspective of tangleGen on the composition and structure of populations improves the interpretability of the inferred ancestral relationships. Moreover, tangleGen adds a new layer of explainability, as it allows identifying the SNPs that are responsible for the clustering structure. We demonstrate the capabilities and benefits of tangleGen for the inference of ancestral relationships, using both simulated data and data from the 1000 Genomes Project.

Scheduling Cluster Tools with Multi-Space Process Modules and a Multi-Finger-Arm Robot in Wafer Fabrication Subject to Wafer Residency Time Constraints

Scheduling Cluster Tools with Multi-Space Process Modules and a Multi-Finger-Arm Robot in Wafer Fabrication Subject to Wafer Residency Time Constraints

Applying rearrangement distances to enable plasmid epidemiology with pling.

Plasmids are a key vector of antibiotic resistance, but the current bioinformatics toolkit is not well suited to tracking them. The rapid structural changes seen in plasmid genomes present considerable challenges to evolutionary and epidemiological analysis. Typical approaches are either low resolution (replicon typing) or use shared k-mer content to define a genetic distance. However, this distance can both overestimate plasmid relatedness by ignoring rearrangements, and underestimate by over-penalizing gene gain/loss. Therefore a model is needed which captures the key components of how plasmid genomes evolve structurally - through gene/block gain or loss, and rearrangement. A secondary requirement is to prevent promiscuous transposable elements (TEs) leading to over-clustering of unrelated plasmids. We choose the 'Double Cut and Join Indel' (DCJ-Indel) model, in which plasmids are studied at a coarse level, as a sequence of signed integers (representing genes or aligned blocks), and the distance between two plasmids is the minimum number of rearrangement events or indels needed to transform one into the other. We show how this gives much more meaningful distances between plasmids. We introduce a software workflow pling (https://github.com/iqbal-lab-org/pling), which uses the DCJ-Indel model, to calculate distances between plasmids and then cluster them. In our approach, we combine containment distances and DCJ-Indel distances to build a TE-aware plasmid network. We demonstrate superior performance and interpretability to other plasmid clustering tools on the 'Russian Doll' dataset and a hospital transmission dataset.

Collaborative Scheduling for Single-Arm Cluster Tools With an Equipment Front-End Module Subject to Chamber Cleaning Requirements

Collaborative Scheduling for Single-Arm Cluster Tools With an Equipment Front-End Module Subject to Chamber Cleaning Requirements

AptamerRunner: An accessible aptamer structure prediction and clustering algorithm for visualization of selected aptamers

Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for targets and are generated using the iterative Systematic Evolution of Ligands by EXponential enrichment (SELEX) process. Next-generation sequencing (NGS) revolutionized aptamer selections by allowing a more comprehensive analysis of SELEX-enriched aptamers as compared to Sanger sequencing. The current challenge with aptamer NGS datasets is identifying a diverse cohort of candidate aptamers with the highest likelihood of successful experimental validation. Herein we present AptamerRunner, an aptamer sequence and/or structure clustering algorithm that synergistically integrates computational analysis with visualization and expertise-directed decision making. The visual integration of networked aptamers with ranking data, such as fold enrichment or scoring algorithm results, represents a significant advancement over existing clustering tools by providing a natural context to depict groups of aptamers from which ranked or scored candidates can be chosen for experimental validation. The inherent flexibility, user-friendly design, and prospects for future enhancements with AptamerRunner has broad-reaching implications for aptamer researchers across a wide range of disciplines.

A clustering tool for generating biological geometries for computational modeling in radiobiology.

To develop a computational tool that converts biological images into geometries compatible with computational software dedicated to the Monte Carlo simulation of radiation transport (TOPAS), and subsequent biological tissue responses (CompuCell3D). The depiction of individual biological entities from segmentation images is essential in computational radiobiological modeling for two reasons: image pixels or voxels representing a biological structure, like a cell, should behave as a single entity when simulating biological processes, and the action of radiation in tissues is described by the association of biological endpoints to physical quantities, as radiation dose, scored the entire group of voxels assembling a cell.
Approach: The tool is capable of cropping and resizing the images and performing clustering of image voxels to create independent entities (clusters) by assigning a unique identifier to these voxels conforming to the same cluster. The clustering algorithm is based on the adjacency of voxels with image values above an intensity threshold to others already assigned to a cluster. The performance of the tool to generate geometries that reproduced original images was evaluated by the Dice Similarity Coefficient (DSC), and by the number of individual entities in both geometries. A set of tests consisting of segmentation images of cultured neuroblastoma cells, two cell nucleus populations, and the vasculature of a mouse brain were used.
Main results: The DSC was 1.0 in all images, indicating that original and generated geometries were identical, and the number of individual entities in both geometries agreed, proving the ability of the tool to cluster voxels effectively following user-defined specifications. The potential of this tool in computational radiobiological modeling, was shown by evaluating the spatial distribution of DNA Double-Strand-Breaks after microbeam irradiation in a segmentation image of a cell culture.
Significance: This tool enables the use of realistic biological geometries in computational radiobiological studies.

Graph contrastive learning as a versatile foundation for advanced scRNA-seq data analysis.

Single-cell RNA sequencing (scRNA-seq) offers unprecedented insights into transcriptome-wide gene expression at the single-cell level. Cell clustering has been long established in the analysis of scRNA-seq data to identify the groups of cells with similar expression profiles. However, cell clustering is technically challenging, as raw scRNA-seq data have various analytical issues, including high dimensionality and dropout values. Existing research has developed deep learning models, such as graph machine learning models and contrastive learning-based models, for cell clustering using scRNA-seq data and has summarized the unsupervised learning of cell clustering into a human-interpretable format. While advances in cell clustering have been profound, we are no closer to finding a simple yet effective framework for learning high-quality representations necessary for robust clustering. In this study, we propose scSimGCL, a novel framework based on the graph contrastive learning paradigm for self-supervised pretraining of graph neural networks. This framework facilitates the generation of high-quality representations crucial for cell clustering. Our scSimGCL incorporates cell-cell graph structure and contrastive learning to enhance the performance of cell clustering. Extensive experimental results on simulated and real scRNA-seq datasets suggest the superiority of the proposed scSimGCL. Moreover, clustering assignment analysis confirms the general applicability of scSimGCL, including state-of-the-art clustering algorithms. Further, ablation study and hyperparameter analysis suggest the efficacy of our network architecture with the robustness of decisions in the self-supervised learning setting. The proposed scSimGCL can serve as a robust framework for practitioners developing tools for cell clustering. The source code of scSimGCL is publicly available at https://github.com/zhangzh1328/scSimGCL.

Periodic Scheduling Optimization for Dual-Arm Cluster Tools with Arm Task and Residency Time Constraints via Petri Net Model

In order to improve quality assurance in wafer manufacturing, there are strict process requirements. Besides the well-known residency time constraints (RTCs), a dual-arm cluster tool also requires each robot arm to execute a specific set of tasks. We call such a tool an arm task-constrained dual-arm cluster tool (ATC-DACT). To do this, one of the arms is identified as the dirty one and the other as the clean one. The dirty one can deal with raw wafers, while the clean one can deal with processed wafers. This requirement raises a new problem for scheduling a cluster tool. This paper discusses the scheduling problem of ATC-DACTs with RTCs. Due to the arm task constraints, the proven, effective swap strategy is no longer applicable to ATC-DACTs, making the scheduling problem difficult. To address this problem, we explicitly describe the robot waiting as an event and build a Petri net (PN) model. Then, we propose a hybrid task sequence (HTS) as an operation strategy by combining the swap and backward strategies. Based on the HTS, the necessary and sufficient conditions for schedulability are established; also, a linear programming model is developed. We then develop an algorithm using these results to optimally schedule the system. Industrial case studies demonstrate the application of this method.

Longitudinal analysis of peripheral immune cells in patients with multiple sclerosis treated with anti-CD20 therapy.

Anti-CD20 therapy is a highly effective treatment for multiple sclerosis (MS). In this study, we investigated MS-related changes in peripheral blood mononuclear cell (PBMC) subsets compared to healthy controls and longitudinal changes related to the treatment. Multicolor spectral flow cytometry analysis was performed on 78 samples to characterize disease- and treatment-related PBMC clusters. Blood samples from MS patients were collected at baseline and up to 8 months post-treatment, with three collection points after treatment initiation. Unsupervised clustering tools and manual gating were applied to identify subclusters of interest and quantify changes. B cells were depleted from the periphery after anti-CD20 treatment as expected, and we observed an isolated acute, transitory drop in the proportion of natural killer (NK) and NKTcells among the main populations of PBMC (P = 0.03, P = 0.004). Major affected PBMC subpopulations were cytotoxic immune cells (NK, NKT, and CD8+ Tcells), and we observed a higher proportion of cytotoxic cells with reduced brain-homing ability and a higher regulatory function as a long-term anti-CD20-related effect. Additionally, anti-CD20 therapy altered distributions of memory CD8+ Tcells and reduced exhaustion markers in both CD4+ and CD8+ Tcells. The findings of this study elucidate phenotypic clusters of NK and CD8+ Tcells, which have previously been underexplored in the context of anti-CD20 therapy. Phenotypic modifications towards a more regulatory and controlled phenotype suggest that these subpopulations may play a critical and previously unrecognized role in mediating the therapeutic efficacy of anti-CD20 treatments.

ImmCellTyper facilitates systematic mass cytometry data analysis for deep immune profiling.

Mass cytometry is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level, advancing clinical research in immune monitoring. Nevertheless, the vast data generated by cytometry by time-of-flight (CyTOF) poses a significant analytical challenge. To address this, we describe ImmCellTyper (https://github.com/JingAnyaSun/ImmCellTyper), a novel toolkit for CyTOF data analysis. This framework incorporates BinaryClust, an in-house developed semi-supervised clustering tool that automatically identifies main cell types. BinaryClust outperforms existing clustering tools in accuracy and speed, as shown in benchmarks with two datasets of approximately 4 million cells, matching the precision of manual gating by human experts. Furthermore, ImmCellTyper offers various visualisation and analytical tools, spanning from quality control to differential analysis, tailored to users' specific needs for a comprehensive CyTOF data analysis solution. The workflow includes five key steps: (1) batch effect evaluation and correction, (2) data quality control and pre-processing, (3) main cell lineage characterisation and quantification, (4) in-depth investigation of specific cell types; and (5) differential analysis of cell abundance and functional marker expression across study groups. Overall, ImmCellTyper combines expert biological knowledge in a semi-supervised approach to accurately deconvolute well-defined main cell lineages, while maintaining the potential of unsupervised methods to discover novel cell subsets, thus facilitating high-dimensional immune profiling.

Anomaly Detection for Power Quality Analysis Using Smart Metering Systems.

The problem of Power Quality analysis is becoming crucial to ensuring the proper functioning of complex systems and big plants. In this regard, it is essential to rapidly detect anomalies in voltage and current signals to ensure a prompt response and maximize the system's availability with the minimum maintenance cost. In this paper, anomaly detection algorithms based on machine learning, such as One Class Support Vector Machine (OCSVM), Isolation Forest (IF), and Angle-Based Outlier Detection (ABOD), are used as a first tool for rapid and effective clustering of the measured voltage and current signals directly on-line on the sensing unit. If the proposed anomaly detection algorithm detects an anomaly, further investigations using suitable classification algorithms are required. The main advantage of the proposed solution is the ability to rapidly and efficiently detect different types of anomalies with low computational complexity, allowing the implementation of the algorithm directly on the sensor node used for signal acquisition. A suitable experimental platform has been established to evaluate the advantages of the proposed method. All the different models were tested using a consistent set of hyperparameters and an output dataset generated from the principal component analysis technique. The best results achieved included models reaching 100% recall and a 92% F1 score.

ScVSC: Deep Variational Subspace Clustering for Single-Cell Transcriptome Data.

Single-cell RNA sequencing (scRNA-seq) is a potent advancement for analyzing gene expression at the individual cell level, allowing for the identification of cellular heterogeneity and subpopulations. However, it suffers from technical limitations that result in sparse and heterogeneous data. Here, we propose scVSC, an unsupervised clustering algorithm built on deep representation neural networks. The method incorporates the variational inference into the subspace model, which imposes regularization constraints on the latent space and further prevents overfitting. In a series of experiments across multiple datasets, scVSC outperforms existing state-of-the-art unsupervised and semi-supervised clustering tools regarding clustering accuracy and running efficiency. Moreover, the study indicates that scVSC could visually reveal the state of trajectory differentiation, accurately identify differentially expressed genes, and further discover biologically critical pathways.

Comparable clinical advantages identification of three formulae on rheumatic disease using a modular-based network proximity approach

Ethnopharmacological relevanceHerbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. Aim of this studyTo develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. Materials and methodsIn this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. Results32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = −20.26); YXB was significantly associated with AS (Z = −4.532), MI (Z = −29.11), RhFv (Z = −6.945), OA (Z = −39.97), and GA (Z = −13.03); and WBFK was significantly associated with MI (Z = −205.5), SLE (Z = −37.65), RhFv (Z = −42.45), and GA (Z = −17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. ConclusionsThe modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI’s robust and consistent performance.

Exploration of small molecule compounds targeting abdominal aortic aneurysm based on CMap database and molecular dynamics simulation.

The mitigation of abdominal aortic aneurysm (AAA) growth through pharmaceutical intervention offers the potential to avert the perils associated with AAA rupture and the subsequent need for surgical intervention. Nevertheless, the existing effective drugs for AAA treatment are limited, necessitating a pressing exploration for novel therapeutic medications. AAA-related transcriptome data were downloaded from GEO, and differentially expressed genes (DEGs) in AAA tissue were screened for GO and KEGG enrichment analyses. Small molecule compounds and their target proteins with negative connectivity to the AAA expression profile were predicted in the Connectivity Map (CMap) database. Molecular docking and molecular dynamics simulation were performed to predict the binding of the target protein to the small molecule compound, and the MM/GBSA method was used to calculate the binding free energy. Cluster analysis was performed using the cluster tool in the GROMACS package. An AAA cell-free model was built, and CETSA experiments were used to demonstrate the binding ability of small molecules to the target protein in cells. A total of 2244 DEGs in AAA were obtained through differential analysis, and the DEGs were mainly enriched in the tubulin binding biological function and cell cycle pathway. The CMap results showed that Apicidin had a potential therapeutic effect on AAA with a connectivity score of -97.74, and HDAC4 was the target protein of Apicidin. Based on literature, HDAC4-Apicidin was selected as the subsequent research object. The lowest affinity of Apicidin-HDAC4 molecular docking was -8.218kcal/mol. Molecular dynamics simulation results indicated that Apicidin-HDAC4 could form a stable complex. MM/GBSA analysis showed a total binding free energy of -55.40 ± 0.79kcal/mol, and cluster analysis showed that there were two main conformational clusters during the binding process, accounting for 22.4% and 57.8%, respectively. Apicidin could form hydrogen bonds with surrounding residues for stable binding. CETSA experiment proved the stable binding ability of Apicidin and HDAC4. Apicidin inhibited HDAC4 in AAA and exhibited favorable protein-ligand interactions and stability, making it a potential candidate drug for treating AAA.

Scheduling of Time-Constrained Single-Arm Cluster Tools with Two-Space Process Modules in Semiconductor Manufacturing

Scheduling of Time-Constrained Single-Arm Cluster Tools with Two-Space Process Modules in Semiconductor Manufacturing

Single Window Search System for Libraries using VuFind

The main objective of this study is to develop methods for enhancing the search capabilities of library collections by integrating various technological elements. Implementing this functional enhancement will provide users access to modern services and resources. The single-window search mechanism is created and built on the VuFind open-source discovery tool. The common access window has been created after properly configuring ILS-OPAC Koha, CONTENTdm, Digital Commons, DSpace, EPrints, Fedora, Greenstone, Omeka, and OPUS. It is based on LAMP architecture and uses Apache Solr, Tomcat, and Apache Tika to create indexes for easy document search through VuFind. This study suggests a new way to easily search and collect data from different domain-specific cluster tools using a single interface. This domain-specific framework provides an ideal environment for libraries to develop large-scale library discovery services. The originality of this paper lies in creating a prototype integrated framework to facilitate the easy installation and configuration of VuFind for integrating domain-specific software in both ILS and IDR.