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Abstract Background The results of high-throughput biology (‘omic’) experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival. However, an opportunity remains for open-source software that can archive and present the results of omic analyses with broad accommodation of study-specific analytical approaches and visualizations with useful exploration features. Results We present OmicNavigator, an R package for the archival, visualization and interactive exploration of omic studies. OmicNavigator enables bioinformaticians to create web applications that interactively display their custom visualizations and analysis results linked with app-derived analytical tools, graphics, and tables. Studies created with OmicNavigator can be viewed within an interactive R session or hosted on a server for shared access. Conclusions OmicNavigator can be found at https://github.com/abbvie-external/OmicNavigator

Background: The results of high-throughput biology ('omic') experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival. However, an opportunity remains for open-source software that can archive and present the results of omic analyses with broad accommodation of study-specific analytical approaches and visualizations with useful exploration features. Results: We present OmicNavigator, an R package for the archival, visualization and interactive exploration of omic studies. OmicNavigator enables bioinformaticians to create web applications that interactively display their custom visualizations and analysis results linked with app-derived analytical tools, graphics, and tables. Studies created with OmicNavigator can be viewed within an interactive R session or hosted on a server for shared access. Conclusions: OmicNavigator can be found at https://github.com/abbvie-external/OmicNavigator [ABSTRACT FROM AUTHOR]

Abstract Background: The development of single-cell technologies yields large datasets of information as diverse and multimodal as transcriptomes, immunophenotypes, and spatial position from tissue sections in the so-called ’spatial transcriptomics’. Currently however, user-friendly, powerful, and free algorithmic tools for straightforward analysis of spatial transcriptomic datasets are scarce. Results: Here, we introduce Single-Cell Spatial Explorer, an open-source software for multimodal exploration of spatial transcriptomics, examplified with 9 human and murine tissues datasets from 4 different technologies. Conclusions: Single-Cell Spatial Explorer is a very powerful, versatile, and interoperable tool for spatial transcriptomics analysis.

BACKGROUND:Large image datasets acquired on automated microscopes typically have some fraction of low quality, out-of-focus images, despite the use of hardware autofocus systems. Identification of these images using automated image analysis with high accuracy is important for obtaining a clean, unbiased image dataset. Complicating this task is the fact that image focus quality is only well-defined in foreground regions of images, and as a result, most previous approaches only enable a computation of the relative difference in quality between two or more images, rather than an absolute measure of quality. RESULTS:We present a deep neural network model capable of predicting an absolute measure of image focus on a single image in isolation, without any user-specified parameters. The model operates at the image-patch level, and also outputs a measure of prediction certainty, enabling interpretable predictions. The model was trained on only 384 in-focus Hoechst (nuclei) stain images of U2OS cells, which were synthetically defocused to one of 11 absolute defocus levels during training. The trained model can generalize on previously unseen real Hoechst stain images, identifying the absolute image focus to within one defocus level (approximately 3 pixel blur diameter difference) with 95% accuracy. On a simpler binary in/out-of-focus classification task, the trained model outperforms previous approaches on both Hoechst and Phalloidin (actin) stain images (F-scores of 0.89 and 0.86, respectively over 0.84 and 0.83), despite only having been presented Hoechst stain images during training. Lastly, we observe qualitatively that the model generalizes to two additional stains, Hoechst and Tubulin, of an unseen cell type (Human MCF-7) acquired on a different instrument. CONCLUSIONS:Our deep neural network enables classification of out-of-focus microscope images with both higher accuracy and greater precision than previous approaches via interpretable patch-level focus and certainty predictions. The use of synthetically defocused images precludes the need for a manually annotated training dataset. The model also generalizes to different image and cell types. The framework for model training and image prediction is available as a free software library and the pre-trained model is available for immediate use in Fiji (ImageJ) and CellProfiler.

Background: The development of single-cell technologies yields large datasets of information as diverse and multimodal as transcriptomes, immunophenotypes, and spatial position from tissue sections in the so-called 'spatial transcriptomics'. Currently however, user-friendly, powerful, and free algorithmic tools for straightforward analysis of spatial transcriptomic datasets are scarce. Results: Here, we introduce Single-Cell Spatial Explorer, an open-source software for multimodal exploration of spatial transcriptomics, examplified with 9 human and murine tissues datasets from 4 different technologies. Conclusions: Single-Cell Spatial Explorer is a very powerful, versatile, and interoperable tool for spatial transcriptomics analysis. [ABSTRACT FROM AUTHOR]

Motivation: Aberrant DNA methylation in transcription factor binding sites has been shown to lead to anomalous gene regulation that is strongly associated with human disease. However, the majority of methylation-sensitive positions within transcription factor binding sites remain unknown. Here we introduce SEMplMe, a computational tool to generate predictions of the effect of methylation on transcription factor binding strength in every position within a transcription factor's motif. Results: SEMplMe uses ChIP-seq and whole genome bisulfite sequencing to predict effects of methylation within binding sites. SEMplMe validates known methylation sensitive and insensitive positions within a binding motif, identifies cell type specific transcription factor binding driven by methylation, and outperforms SELEX-based predictions for CTCF. These predictions can be used to identify aberrant sites of DNA methylation contributing to human disease. Availability and Implementation: SEMplMe is available from https://github.com/Boyle-Lab/SEMplMe. [ABSTRACT FROM AUTHOR]

Abstract Background The biomedical literature is expanding at ever-increasing rates, and it has become extremely challenging for researchers to keep abreast of new data and discoveries even in their own domains of expertise. We introduce PaperBot, a configurable, modular, open-source crawler to automatically find and efficiently index peer-reviewed publications based on periodic full-text searches across publisher web portals. Results PaperBot may operate stand-alone or it can be easily integrated with other software platforms and knowledge bases. Without user interactions, PaperBot retrieves and stores the bibliographic information (full reference, corresponding email contact, and full-text keyword hits) based on pre-set search logic from a wide range of sources including Elsevier, Wiley, Springer, PubMed/PubMedCentral, Nature, and Google Scholar. Although different publishing sites require different search configurations, the common interface of PaperBot unifies the process from the user perspective. Once saved, all information becomes web accessible allowing efficient triage of articles based on their actual relevance and seamless annotation of suitable metadata content. The platform allows the agile reconfiguration of all key details, such as the selection of search portals, keywords, and metadata dimensions. The tool also provides a one-click option for adding articles manually via digital object identifier or PubMed ID. The microservice architecture of PaperBot implements these capabilities as a loosely coupled collection of distinct modules devised to work separately, as a whole, or to be integrated with or replaced by additional software. All metadata is stored in a schema-less NoSQL database designed to scale efficiently in clusters by minimizing the impedance mismatch between relational model and in-memory data structures. Conclusions As a testbed, we deployed PaperBot to help identify and manage peer-reviewed articles pertaining to digital reconstructions of neuronal morphology in support of the NeuroMorpho.Org data repository. PaperBot enabled the custom definition of both general and neuroscience-specific metadata dimensions, such as animal species, brain region, neuron type, and digital tracing system. Since deployment, PaperBot helped NeuroMorpho.Org more than quintuple the yearly volume of processed information while maintaining a stable personnel workforce.

Background: The biomedical literature is expanding at ever-increasing rates, and it has become extremely challenging for researchers to keep abreast of new data and discoveries even in their own domains of expertise. We introduce PaperBot, a configurable, modular, open-source crawler to automatically find and efficiently index peer-reviewed publications based on periodic full-text searches across publisher web portals. Results: PaperBot may operate stand-alone or it can be easily integrated with other software platforms and knowledge bases. Without user interactions, PaperBot retrieves and stores the bibliographic information (full reference, corresponding email contact, and full-text keyword hits) based on pre-set search logic from a wide range of sources including Elsevier, Wiley, Springer, PubMed/PubMedCentral, Nature, and Google Scholar. Although different publishing sites require different search configurations, the common interface of PaperBot unifies the process from the user perspective. Once saved, all information becomes web accessible allowing efficient triage of articles based on their actual relevance and seamless annotation of suitable metadata content. The platform allows the agile reconfiguration of all key details, such as the selection of search portals, keywords, and metadata dimensions. The tool also provides a one-click option for adding articles manually via digital object identifier or PubMed ID. The microservice architecture of PaperBot implements these capabilities as a loosely coupled collection of distinct modules devised to work separately, as a whole, or to be integrated with or replaced by additional software. All metadata is stored in a schema-less NoSQL database designed to scale efficiently in clusters by minimizing the impedance mismatch between relational model and in-memory data structures. Conclusions: As a testbed, we deployed PaperBot to help identify and manage peer-reviewed articles pertaining to digital reconstructions of neuronal morphology in support of the NeuroMorpho.Org data repository. PaperBot enabled the custom definition of both general and neuroscience-specific metadata dimensions, such as animal species, brain region, neuron type, and digital tracing system. Since deployment, PaperBot helped NeuroMorpho.Org more than quintuple the yearly volume of processed information while maintaining a stable personnel workforce. [ABSTRACT FROM AUTHOR]

Background: No gold standard exists in the world of scientific image acquisition; a proliferation of instruments each with its own proprietary data format has made out-of-the-box sharing of that data nearly impossible. In the field of light microscopy, the Bio-Formats library was designed to translate such proprietary data formats to a common, open-source schema, enabling sharing and reproduction of scientific results. While Bio-Formats has proved successful for microscopy images, the greater scientific community was lacking a domain-independent framework for format translation. Results: SCIFIO (SCientific Image Format Input and Output) is presented as a freely available, open-source library unifying the mechanisms of reading and writing image data. The core of SCIFIO is its modular definition of formats, the design of which clearly outlines the components of image I/O to encourage extensibility, facilitated by the dynamic discovery of the SciJava plugin framework. SCIFIO is structured to support coexistence of multiple domain-specific open exchange formats, such as Bio-Formats' OME-TIFF, within a unified environment. Conclusions: SCIFIO is a freely available software library developed to standardize the process of reading and writing scientific image formats. [ABSTRACT FROM AUTHOR]

Background: Cancer immunotherapy has recently entered a remarkable renaissance phase with the approval of several agents for treatment. Cancer treatment platforms have demonstrated profound tumor regressions including complete cure in patients with metastatic cancer. Moreover, technological advances in next-generation sequencing (NGS) as well as the development of devices for scanning whole-slide bioimages from tissue sections and image analysis software for quantitation of tumor-infiltrating lymphocytes (TILs) allow, for the first time, the development of personalized cancer immunotherapies that target patient specific mutations. However, there is currently no bioinformatics solution that supports the integration of these heterogeneous datasets. Results: We have developed a bioinformatics platform – Personalized Oncology Suite (POS) – that integrates clinical data, NGS data and whole-slide bioimages from tissue sections. POS is a web-based platform that is scalable, flexible and expandable. The underlying database is based on a data warehouse schema, which is used to integrate information from different sources. POS stores clinical data, genomic data (SNPs and INDELs identified from NGS analysis), and scanned whole-slide images. It features a genome browser as well as access to several instances of the bioimage management application Bisque. POS provides different visualization techniques and offers sophisticated upload and download possibilities. The modular architecture of POS allows the community to easily modify and extend the application. Conclusions: The web-based integration of clinical, NGS, and imaging data represents a valuable resource for clinical researchers and future application in medical oncology. POS can be used not only in the context of cancer immunology but also in other studies in which NGS data and images of tissue sections are generated. The application is open-source and can be downloaded at http://www.icbi.at/POS. [ABSTRACT FROM AUTHOR]

Background: The analysis of large, complex networks is an important aspect of ongoing biological research. Yet there is a need for entirely new, scalable approaches for network visualization that can provide more insight into the structure and function of these complex networks. Results: To address this need, we have developed a software tool named BioFabric, which uses a novel network visualization technique that depicts nodes as one-dimensional horizontal lines arranged in unique rows. This is in distinct contrast to the traditional approach that represents nodes as discrete symbols that behave essentially as zero-dimensional points. BioFabric then depicts each edge in the network using a vertical line assigned to its own unique column, which spans between the source and target rows, i.e. nodes. This method of displaying the network allows a full-scale view to be organized in a rational fashion; interesting network structures, such as sets of nodes with similar connectivity, can be quickly scanned and visually identified in the full network view, even in networks with well over 100,000 edges. This approach means that the network is being represented as a fundamentally linear, sequential entity, where the horizontal scroll bar provides the basic navigation tool for browsing the entire network. Conclusions: BioFabric provides a novel and powerful way of looking at any size of network, including very large networks, using horizontal lines to represent nodes and vertical lines to represent edges. It is freely available as an open-source Java application. [ABSTRACT FROM AUTHOR]