The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large language model (LLM). Completed workflows are compatible with Common Workflow Language (CWL) and can be published as research publications, slideshows, and posters. To demonstrate how the PWB generates meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases prioritizes drug targets for individual cancer patients using data from the NIH Common Fund programs GTEx, LINCS, Metabolomics, GlyGen, and ExRNA. The workflows created with PWB can be repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/.

The L1000 technology, a cost-effective high-throughput transcriptomics technology, has been applied to profile a collection of human cell lines for their gene expression response to > 30,000 chemical and genetic perturbations. In total, there are currently over 3 million available L1000 profiles. Such a dataset is invaluable for the discovery of drug and target candidates and for inferring mechanisms of action for small molecules. The L1000 assay only measures the mRNA expression of 978 landmark genes while 11,350 additional genes are computationally reliably inferred. The lack of full genome coverage limits knowledge discovery for half of the human protein coding genes, and the potential for integration with other transcriptomics profiling data. Here we present a Deep Learning two-step model that transforms L1000 profiles to RNA-seq-like profiles. The input to the model are the measured 978 landmark genes while the output is a vector of 23,614 RNA-seq-like gene expression profiles. The model first transforms the landmark genes into RNA-seq-like 978 gene profiles using a modified CycleGAN model applied to unpaired data. The transformed 978 RNA-seq-like landmark genes are then extrapolated into the full genome space with a fully connected neural network model. The two-step model achieves 0.914 Pearson's correlation coefficients and 1.167 root mean square errors when tested on a published paired L1000/RNA-seq dataset produced by the LINCS and GTEx programs. The processed RNA-seq-like profiles are made available for download, signature search, and gene centric reverse search with unique case studies.

BACKGROUND: PubMed contains millions of abstracts that co-mention terms that describe drugs with other biomedical terms such as genes or diseases. Unique opportunities exist for leveraging these co-mentions by integrating them with other drug-drug similarity resources such as the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 signatures to develop novel hypotheses. RESULTS: DrugShot is a web-based server application and an Appyter that enables users to enter any biomedical search term into a simple input form to receive ranked lists of drugs and other small molecules based on their relevance to the search term. To produce ranked lists of small molecules, DrugShot cross-references returned PubMed identifiers (PMIDs) with DrugRIF or AutoRIF, which are curated resources of drug-PMID associations, to produce an associated small molecule list where each small molecule is ranked according to total co-mentions with the search term from shared PubMed IDs. Additionally, using two types of drug-drug similarity matrices, lists of small molecules are predicted to be associated with the search term. Such predictions are based on literature co-mentions and signature similarity from LINCS L1000 drug-induced gene expression profiles. CONCLUSIONS: DrugShot prioritizes drugs and small molecules associated with biomedical search terms. In addition to listing known associations, DrugShot predicts additional drugs and small molecules related to any search term. Hence, DrugShot can be used to prioritize drugs and preclinical compounds for drug repurposing and suggest indications and adverse events for preclinical compounds. DrugShot is freely and openly available at: https://maayanlab.cloud/drugshot and https://appyters.maayanlab.cloud/#/DrugShot .

MOTIVATION: Micro-blogging with Twitter to communicate new results, discuss ideas and share techniques is becoming central. While most Twitter users are real people, the Twitter API provides the opportunity to develop Twitter bots and to analyze global trends in tweets. RESULTS: EnrichrBot is a bot that tracks and tweets information about human genes implementing six principal functions: (i) tweeting information about under-studied genes including non-coding lncRNAs, (ii) replying to requests for information about genes, (iii) responding to GWASbot, another bot that tweets Manhattan plots from genome-wide association study analysis of the UK Biobank, (iv) tweeting randomly selected gene sets from the Enrichr database for analysis with Enrichr, (v) responding to mentions of human genes in tweets with additional information about these genes and (vi) tweeting a weekly report about the most trending genes on Twitter. AVAILABILITY AND IMPLEMENTATION: https://twitter.com/botenrichr; source code: https://github.com/MaayanLab/EnrichrBot. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In our earlier work, we presented BOAT, a big-data open source analytics toolkit and framework, and applied it to analyze trends and outliers in public healthcare data. In this paper, we extend this framework to predict the costs of different medical procedures that patients could incur, based on open healthcare data. Specifically, we analyze de-identified patient data from New York State SPARCS (statewide planning and research cooperative system), consisting of more than 2 million records. We investigated the three model classes consisting of multiple linear regression, regression trees and deep neural networks (DNNs). We conducted a grid-search to identify the best parameter choices. We determined that the best performance based on grid-search cross validation with the widely used R2metric was achieved by an 8 layered DNN with size 5x5x10x25x25x10x5x5 using an Adam optimizer with learning rate of 0.01. We obtained an R2value of 0.71 which is better than the values reported in the literature for similar problems.

The interactive exploration of large and evolving datasets is challenging as relationships between underlying variables may not be fully understood. There may be hidden trends and patterns in the data that are worthy of further exploration and analysis. We present a system that methodically explores multiple combinations of variables using a searchlight subsect scan algorithm to identify outliers. An iterative k-means clustering algorithm is applied to features derived through a split-apply-combine paradigm used in the database literature. Outliers are identified as singleton or small clusters. This algorithm is swept across the dataset in a searchlight manner. The dimensions that contain outliers are combined with other dimensions using an efficient subset scan technique to gain further insight into the outliers. We illustrate this system by analyzing open health care data released by New York State. We apply our iterative k-means searchlight followed by subset scanning. Several anomalous trends in the data are identified, including cost overruns at specific hospitals, and increases in diagnoses such as suicides. These constitute novel findings in the literature, and are of potential use to regulatory agencies, policy makers and concerned citizens.

When analyzing data where the relationships between variables are not fully understood, it is typical to engage in visual exploration. However, this is slow and manually intensive, and interesting trends could potentially be missed. Ideally, we would like to focus on patterns and locations within the data that are interesting, such as significant clusters and outliers. We present a novel iterative k-means clustering algorithm to efficiently identify clusters in large datasets. This facilitates rapid visual exploration of new datasets. We illustrate our framework by performing a detailed analysis of open health care data released by the US Government and New York State. We apply our iterative k-means algorithm to identify clusters of trends in labor force participation to present a unique perspective by area of medical specialty over a 50-year period. Specialties such as nurse practitioners have seen a significant increase in the number of practitioners relative to internal medicine. Our code is open source and available on Github.