The reconstruction of transcriptional regulatory networks (TRNs) is a long-standing challenge in human genetics. Numerous computational methods have been developed to infer regulatory interactions between human transcriptional factors (TFs) and target genes from high-throughput data, and their performance evaluation requires gold-standard interactions. Here we present a database of literature-curated human TF-target interactions, TRRUST (transcriptional regulatory relationships unravelled by sentence-based text-mining, http://www.grnpedia.org/trrust), which currently contains 8,015 interactions between 748 TF genes and 1,975 non-TF genes. A sentence-based text-mining approach was employed for efficient manual curation of regulatory interactions from approximately 20 million Medline abstracts. To the best of our knowledge, TRRUST is the largest publicly available database of literature-curated human TF-target interactions to date. TRRUST also has several useful features: i) information about the mode-of-regulation; ii) tests for target modularity of a query TF; iii) tests for TF cooperativity of a query target; iv) inferences about cooperating TFs of a query TF; and v) prioritizing associated pathways and diseases with a query TF. We observed high enrichment of TF-target pairs in TRRUST for top-scored interactions inferred from high-throughput data, which suggests that TRRUST provides a reliable benchmark for the computational reconstruction of human TRNs.

Increasingly, highly multiplexed tissue imaging methods are used to profile protein expression at the single-cell level. However, a critical limitation is the lack of robust cell segmentation tools for tissue sections. We present Multiplexed Image Resegmentation of Internal Aberrant Membranes (MIRIAM) that combines (a) a pipeline for cell segmentation and quantification that incorporates machine learning-based pixel classification to define cellular compartments, (b) a novel method for extending incomplete cell membranes, and (c) a deep learning-based cell shape descriptor. Using human colonic adenomas as an example, we show that MIRIAM is superior to widely utilized segmentation methods and provides a pipeline that is broadly applicable to different imaging platforms and tissue types.

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Increasingly, highly multiplexed in situ tissue imaging methods are used to profile protein expression at the single-cell level. However, a critical limitation is a lack of robust cell segmentation tools applicable for sections of tissues with a complex architecture and multiple cell types. Using human colorectal adenomas, we present a pipeline for cell segmentation and quantification that utilizes machine learning-based pixel classification to define cellular compartments, a novel method for extending incomplete cell membranes, quantification of antibody staining, and a deep learning-based cell shape descriptor. We envision that this method can be broadly applied to different imaging platforms and tissue types.