Dataset Information

3Scover: Identifying Safeguard TF from Cell Type-TF Specificity Network by an Extended Minimum Set Cover Model.

ABSTRACT: Transcription factors (TFs) define cellular identity either by activating target cell program or by silencing donor program as demonstrated by intensive cell reprogramming studies. Here, we propose an extended minimum set cover model with stable selection (3Scover) to systematically identify silencing TFs, named safeguard TFs, from omics data. First, a cell type-TF specificity network is constructed to systematically link cell types with their specifically expressed TFs. Then we search the minimum TF set to cover this network with "many but one specificity" characteristic and integrate many subsampling models for a stable solution. 3Scover identified 30 safeguard TFs in human and mouse. These safeguard TFs are significantly enriched in the experimentally discovered reprogramming panel with their protein-protein interactors. In addition, they tend to interact closely with chromatin regulators, negatively regulate transcription, and function earlier in development. Collectively, 3Scover allows us to probe master TFs and combinatorial regulation in controlling cell identity.

SUBMITTER: Yuan Q

PROVIDER: S-EPMC7303665 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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3Scover: Identifying Safeguard TF from Cell Type-TF Specificity Network by an Extended Minimum Set Cover Model.

Yuan Qiuyue Q Wang Yong Y

iScience 20200602 6

Transcription factors (TFs) define cellular identity either by activating target cell program or by silencing donor program as demonstrated by intensive cell reprogramming studies. Here, we propose an extended minimum set cover model with stable selection (3Scover) to systematically identify silencing TFs, named safeguard TFs, from omics data. First, a cell type-TF specificity network is constructed to systematically link cell types with their specifically expressed TFs. Then we search the minim ...[more]

PMID: 32554189

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Project description:BACKGROUND: Identifying the key transcription factors (TFs) controlling a biological process is the first step toward a better understanding of underpinning regulatory mechanisms. However, due to the involvement of a large number of genes and complex interactions in gene regulatory networks, identifying TFs involved in a biological process remains particularly difficult. The challenges include: (1) Most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation, making it difficult to recognize TFs for a biological process; (2) Transcription usually involves several hundred genes that generate a combination of intrinsic noise from upstream signaling networks and lead to fluctuations in transcription; (3) A TF can function in different cell types or developmental stages. Currently, the methods available for identifying TFs involved in biological processes are still very scarce, and the development of novel, more powerful methods is desperately needed. RESULTS: We developed a computational pipeline called TF-Cluster for identifying functionally coordinated TFs in two steps: (1) Construction of a shared coexpression connectivity matrix (SCCM), in which each entry represents the number of shared coexpressed genes between two TFs. This sparse and symmetric matrix embodies a new concept of coexpression networks in which genes are associated in the context of other shared coexpressed genes; (2) Decomposition of the SCCM using a novel heuristic algorithm termed "Triple-Link", which searches the highest connectivity in the SCCM, and then uses two connected TF as a primer for growing a TF cluster with a number of linking criteria. We applied TF-Cluster to microarray data from human stem cells and Arabidopsis roots, and then demonstrated that many of the resulting TF clusters contain functionally coordinated TFs that, based on existing literature, accurately represent a biological process of interest. CONCLUSIONS: TF-Cluster can be used to identify a set of TFs controlling a biological process of interest from gene expression data. Its high accuracy in recognizing true positive TFs involved in a biological process makes it extremely valuable in building core GRNs controlling a biological process. The pipeline implemented in Perl can be installed in various platforms.

Project description:BackgroundThe minimum data set (MDS) is a collection of data elements to be grouped using a standard approach to allow the use of data for clinical and research purposes. Health data are typically voluminous, complex, and sometimes too ambiguous to generate indicators that can provide knowledge and information on health. This complexity extends further to the rare disease (RD) domain. MDSs are essential for health surveillance as they help provide services and generate recommended population indicators. There is a bottleneck in international literature that reveals a global problem with data collection, recording, and structuring in RD.ObjectiveThis study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them with World Health Organization (WHO) guidelines.MethodsThe population, concept, and context methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. A total of 4 databases were reviewed, and all the processes were reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. The data elements were analyzed, extracted, and organized into 10 categories according to WHO digital health guidelines. The quality assessment used the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist.ResultsWe included 20 studies in our review, 70% (n=14) of which focused on a specific health domain and 30% (n=6) of which referred to RD in general. WHO recommends that health systems and networks use standard terminology to exchange data, information, knowledge, and intelligence in health. However, there was a lack of terminological standardization of the concepts in MDSs. Moreover, the selected studies did not follow the same standard structure for classifying the data from their MDSs. All studies presented MDSs with limitations or restrictions because they covered only a specific RD, or their scope of application was restricted to a specific context or geographic region. Data science methods and clinical experience were used to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks.ConclusionsOur study highlights the difficulties in standardizing and categorizing findings from MDSs for RD because of the varying structures used in different studies. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors. These results can help public policy makers support other aspects of their policies. We highlight the potential of our results to help strategic decisions related to RD.Trial registrationPROSPERO CRD42021221593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221593.International registered report identifier (irrid)RR2-10.1016/j.procs.2021.12.034.

Dataset Information

3Scover: Identifying Safeguard TF from Cell Type-TF Specificity Network by an Extended Minimum Set Cover Model.

Publications

3Scover: Identifying Safeguard TF from Cell Type-TF Specificity Network by an Extended Minimum Set Cover Model.

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