Since its 2009 genesis block, the Bitcoin network has processed >1.08 billion (B) transactions representing >8.72B BTC, offering rich potential for machine learning (ML); yet, its pseudonymity and obscured flow of funds inherent in its UTxO-based design, have rendered this data largely inaccessible for ML research. Addressing this gap, we present an ML-compatible graph modeling the Bitcoin's economic topology by reconstructing the flow of funds. This temporal, heterogeneous graph encompasses complete transaction history up to block 863000, consisting of >2.4B nodes and >39.72B edges. Additionally, we provide custom sampling methods yielding node and edge feature vectors of sampled communities, tools to load and analyze the Bitcoin graph data within specialized graph databases, and ready-to-use database snapshots. This comprehensive dataset and toolkit empower the ML community to tackle Bitcoin's intricate ecosystem at scale, driving progress in applications such as anomaly detection, address classification, market analysis, and large-scale graph ML benchmarking. Dataset and code available at https://github.com/B1AAB/EBA.

BACKGROUND: Protein-DNA binding sites of ChIP-seq experiments are identified where the binding affinity is significant based on a given threshold. The choice of the threshold is a trade-off between conservative region identification and discarding weak, but true binding sites. RESULTS: We rescue weak binding sites using MSPC, which efficiently exploits replicates to lower the threshold required to identify a site while keeping a low false-positive rate, and we compare it to IDR, a widely used post-processing method for identifying highly reproducible peaks across replicates. We observe several master transcription regulators (e.g., SP1 and GATA3) and HDAC2-GATA1 regulatory networks on rescued regions in K562 cell line. CONCLUSIONS: We argue the biological relevance of weak binding sites and the information they add when rescued by MSPC. An implementation of the proposed extended MSPC methodology and the scripts to reproduce the performed analysis are freely available at https://genometric.github.io/MSPC/ ; MSPC is distributed as a command-line application and an R package available from Bioconductor ( https://doi.org/doi:10.18129/B9.bioc.rmspc ).

Supervised machine learning is an essential but difficult to use approach in biomedical data analysis. The Galaxy-ML toolkit (https://galaxyproject.org/community/machine-learning/) makes supervised machine learning more accessible to biomedical scientists by enabling them to perform end-to-end reproducible machine learning analyses at large scale using only a web browser. Galaxy-ML extends Galaxy (https://galaxyproject.org), a biomedical computational workbench used by tens of thousands of scientists across the world, with a suite of tools for all aspects of supervised machine learning.

MOTIVATION: Large biomedical datasets, such as those from genomics and imaging, are increasingly being stored on commercial and institutional cloud computing platforms. This is because cloud-scale computing resources, from robust backup to high-speed data transfer to scalable compute and storage, are needed to make these large datasets usable. However, one challenge for large-scale biomedical data on the cloud is providing secure access, especially when datasets are distributed across platforms. While there are open Web protocols for secure authentication and authorization, these protocols are not in wide use in bioinformatics and are difficult to use for even technologically sophisticated users. RESULTS: We have developed a generic and extensible approach for securely accessing biomedical datasets distributed across cloud computing platforms. Our approach combines OpenID Connect and OAuth2, best-practice Web protocols for authentication and authorization, together with Galaxy (https://galaxyproject.org), a web-based computational workbench used by thousands of scientists across the world. With our enhanced version of Galaxy, users can access and analyze data distributed across multiple cloud computing providers without any special knowledge of access/authorization protocols. Our approach does not require users to share permanent credentials (e.g. username, password, API key), instead relying on automatically generated temporary tokens that refresh as needed. Our approach is generalizable to most identity providers and cloud computing platforms. To the best of our knowledge, Galaxy is the only computational workbench where users can access biomedical datasets across multiple cloud computing platforms using best-practice Web security approaches and thereby minimize risks of unauthorized data access and credential use. AVAILABILITY AND IMPLEMENTATION: Freely available for academic and commercial use under the open-source Academic Free License (https://opensource.org/licenses/AFL-3.0) from the following Github repositories: https://github.com/galaxyproject/galaxy and https://github.com/galaxyproject/cloudauthz.

One-dimensional intervals incremental inverted index (Di4) is a multi-resolution, single-dimension indexing framework for efficient, scalable, and extensible computation of genomic interval expressions. The framework has a tri-layer architecture: the semantic layer provides orthogonal and generic means (including the support of user-defined function) of sense-making and higher-lever reasoning from region-based datasets; the logical layer provides building blocks for region calculus and topological relations between intervals; the physical layer abstracts from persistence technology and makes the model adaptable to variety of persistence technologies, spanning from small-scale (e.g., B+tree) to large-scale (e.g., LevelDB). The extensibility of Di4 to application scenarios is shown with an example of comparative evaluation of ChIP-seq and DNase-Seq replicates. Performance of Di4 is benchmarked for small and large scale scenarios under common bioinformatics application scenarios. Di4 is freely available from https://genometric.github.io/Di4.

Biomedical data exploration requires integrative analyses of large datasets using a diverse ecosystem of tools. For more than a decade, the Galaxy project (https://galaxyproject.org) has provided researchers with a web-based, user-friendly, scalable data analysis framework complemented by a rich ecosystem of tools (https://usegalaxy.org/toolshed) used to perform genomic, proteomic, metabolomic, and imaging experiments. Galaxy can be deployed on the cloud (https://launch.usegalaxy.org), institutional computing clusters, and personal computers, or readily used on a number of public servers (e.g., https://usegalaxy.org). In this paper, we present our plan and progress towards creating Galaxy-as-a-Service-a federation of distributed data and computing resources into a panoptic analysis platform. Users can leverage a pool of public and institutional resources, in addition to plugging-in their private resources, helping answer the challenge of resource divergence across various Galaxy instances and enabling seamless analysis of biomedical data.

Bioinformatics (2015) https://doi.org/10.1093/bioinformatics/btv293 The authors of the above paper wish to inform readers that the source code for the project has been migrated from CodePlex to Github. The correct link to access the source code is: https://github.com/Genometric/MSPC. The paper has now been corrected online.

Enriched region (ER) identification is a fundamental step in several next-generation sequencing (NGS) experiment types. Yet, although NGS experimental protocols recommend producing replicate samples for each evaluated condition and their consistency is usually assessed, typically pipelines for ER identification do not consider available NGS replicates. This may alter genome-wide descriptions of ERs, hinder significance of subsequent analyses on detected ERs and eventually preclude biological discoveries that evidence in replicate could support. MuSERA is a broadly useful stand-alone tool for both interactive and batch analysis of combined evidence from ERs in multiple ChIP-seq or DNase-seq replicates. Besides rigorously combining sample replicates to increase statistical significance of detected ERs, it also provides quantitative evaluations and graphical features to assess the biological relevance of each determined ER set within its genomic context; they include genomic annotation of determined ERs, nearest ER distance distribution, global correlation assessment of ERs and an integrated genome browser. We review MuSERA rationale and implementation, and illustrate how sets of significant ERs are expanded by applying MuSERA on replicates for several types of NGS data, including ChIP-seq of transcription factors or histone marks and DNase-seq hypersensitive sites. We show that MuSERA can determine a new, enhanced set of ERs for each sample by locally combining evidence on replicates, and prove how the easy-to-use interactive graphical displays and quantitative evaluations that MuSERA provides effectively support thorough inspection of obtained results and evaluation of their biological content, facilitating their understanding and biological interpretations. MuSERA is freely available at http://www.bioinformatics.deib.polimi.it/MuSERA/.

BACKGROUND: With the wide-spreading of public repositories of NGS processed data, the availability of user-friendly and effective tools for data exploration, analysis and visualization is becoming very relevant. These tools enable interactive analytics, an exploratory approach for the seamless "sense-making" of data through on-the-fly integration of analysis and visualization phases, suggested not only for evaluating processing results, but also for designing and adapting NGS data analysis pipelines. RESULTS: This paper presents abstractions for supporting the early analysis of NGS processed data and their implementation in an associated tool, named GenoMetric Space Explorer (GeMSE). This tool serves the needs of the GenoMetric Query Language, an innovative cloud-based system for computing complex queries over heterogeneous processed data. It can also be used starting from any text files in standard BED, BroadPeak, NarrowPeak, GTF, or general tab-delimited format, containing numerical features of genomic regions; metadata can be provided as text files in tab-delimited attribute-value format. GeMSE allows interactive analytics, consisting of on-the-fly cycling among steps of data exploration, analysis and visualization that help biologists and bioinformaticians in making sense of heterogeneous genomic datasets. By means of an explorative interaction support, users can trace past activities and quickly recover their results, seamlessly going backward and forward in the analysis steps and comparative visualizations of heatmaps. CONCLUSIONS: GeMSE effective application and practical usefulness is demonstrated through significant use cases of biological interest. GeMSE is available at http://www.bioinformatics.deib.polimi.it/GeMSE/ , and its source code is available at https://github.com/Genometric/GeMSE under GPLv3 open-source license.

MOTIVATION: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) detects genome-wide DNA-protein interactions and chromatin modifications, returning enriched regions (ERs), usually associated with a significance score. Moderately significant interactions can correspond to true, weak interactions, or to false positives; replicates of a ChIP-seq experiment can provide co-localised evidence to decide between the two cases. We designed a general methodological framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with the option to set a significance threshold on the repeated evidence and a minimum number of samples bearing this evidence. RESULTS: We applied our method to Myc transcription factor ChIP-seq datasets in K562 cells available in the ENCODE project. Using replicates, we could extend up to 3 times the ER number with respect to single-sample analysis with equivalent significance threshold. We validated the 'rescued' ERs by checking for the overlap with open chromatin regions and for the enrichment of the motif that Myc binds with strongest affinity; we compared our results with alternative methods (IDR and jMOSAiCS), obtaining more validated peaks than the former and less peaks than latter, but with a better validation. AVAILABILITY AND IMPLEMENTATION: An implementation of the proposed method and its source code under GPLv3 license are freely available at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/, respectively. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary Material are available at Bioinformatics online.

MOTIVATION: Improvement of sequencing technologies and data processing pipelines is rapidly providing sequencing data, with associated high-level features, of many individual genomes in multiple biological and clinical conditions. They allow for data-driven genomic, transcriptomic and epigenomic characterizations, but require state-of-the-art 'big data' computing strategies, with abstraction levels beyond available tool capabilities. RESULTS: We propose a high-level, declarative GenoMetric Query Language (GMQL) and a toolkit for its use. GMQL operates downstream of raw data preprocessing pipelines and supports queries over thousands of heterogeneous datasets and samples; as such it is key to genomic 'big data' analysis. GMQL leverages a simple data model that provides both abstractions of genomic region data and associated experimental, biological and clinical metadata and interoperability between many data formats. Based on Hadoop framework and Apache Pig platform, GMQL ensures high scalability, expressivity, flexibility and simplicity of use, as demonstrated by several biological query examples on ENCODE and TCGA datasets. AVAILABILITY AND IMPLEMENTATION: The GMQL toolkit is freely available for non-commercial use at http://www.bioinformatics.deib.polimi.it/GMQL/.