Faculty and Staff

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

In 2014/2015, Arizona State University (ASU) Libraries, the Labriola National American Indian Data Center, and the ASU American Indian Studies Department completed an ASU Institute for Humanities Research (IHR) seed grant entitled “Carlos Montezuma’s Wassaja Newsletter: Digitization, Access and Context” to digitize all ASU held issues of the newsletter Wassaja Freedom’s Signal for the Indian, which Yavapai activist-intellectual Carlos Montezuma, MD (1866-1923) self-published during 1916-1922. The grant team additionally selected a portion of the ASU Libraries Carlos Montezuma archival collection for digitization to provide a more complete picture of Dr. Carlos Montezuma’s life and work.

The ASU grant team produced a searchable online collection on the ASU Digital Repository and created an online exhibition in conjunction with the IHR Nexus Lab’s Developing Wassaja Project. The Nexus Lab’s role at ASU is to grow the digital humanities through interdisciplinary collaborations bringing together humanities, science, and technology. The Nexus Lab partnered with the grant team to create the Developing Wassaja Project which provided an opportunity for faculty, staff, and students at ASU to engage in electronic publication through web application development.

The resulting web platform, Wassaja: A Carlos Montezuma Project, provides context for this digitized collection and facilitates community interaction, including a partnership with Dr. Montezuma’s home community the Fort McDowell Yavapai Nation. In this webcast, Digital Projects Librarian Matthew Harp, Developing Wassaja Project team member Joe Buenker (subject librarian), and grant team member Joyce Martin (librarian and curator of the Labriola National American Indian Data Center) will discuss and demonstrate the resources created and the resulting partnership with the Fort McDowell Yavapai Nation. The webcast will focus on identifying collaborators and needed skills to engage in Digital Humanities research and on identifying the stages of a collaborative project.

Participants will gain insight on working directly with diverse communities; overcoming technical limitations of traditional institutional repositories; collaborative strategies with faculty, research centers, and cultural heritage societies; solutions for moving hidden collections into an engaging digital exhibition; integrating digital humanities research and instruction with library curation; and preparing for long term costs and management issues.

Anthropology librarian Juliann Couture and Joyce Martin, curator of the Labriola National American Indian Data Center, looking at the Center's display of unique Hopi Kachina dolls. Four of the kachinas (Navan Kachina; Talavi Kachina; Flute Kachina; and Ahöla Kachina) were created by artist, carver, and former ASU employee Tony Dukepoo as a gift to the libraries in 1979. The kachina dolls are on display in the Labriola Center located on the 2nd floor of the Hayden Library on ASU's Tempe campus.

The Simon Ortiz and Labriola Center Lecture on Indigenous Land, Culture, and Community addresses topics and issues across disciplines in the arts, humanities, sciences, and politics. Underscoring Indigenous American experiences and perspectives, this Series seeks to create and celebrate knowledge that evolves from an Indigenous worldview that is inclusive and that is applicable to all walks of life.” Professor Simon Ortiz discussed the overall nature of the Series, especially emphasizing the global nature of Indigenous concerns. Joyce Martin and Matthew Harp elaborated on the contributions of the Labriola National American Indian Data Center and ASU Libraries to the Series.

The Labriola Center hosts an informal event in Hayden Library which facilitates close interaction between the featured speaker and audience members. The ASU Libraries records the evening lectures which take place at the Heard Museum and presents both an audio podcast and streaming video of each lecture on the ASU Library Channel webpage. This lecture series provides not only a chance for community discussion at the events themselves, but through the innovative use of technology the ASU Libraries enables additional forums for discussion in blogs and web pages which choose to link to the streaming videos.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitative trait loci (eQTLs) in a wide range of human tissues/cell types, we identify critical chromatin features that predict variant regulatory potential. We present cepip, a joint likelihood framework, for estimating a variant’s regulatory probability in a context-dependent manner. Our method exhibits significant GWAS signal enrichment and is superior to existing cell type-specific methods. Furthermore, using phenotypically relevant epigenomes to weight the GWAS single-nucleotide polymorphisms, we improve the statistical power of the gene-based association test.

Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-κB) and that inhibition of NF-κB abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-κB exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-κB, thereby inducing HASMC phenotype switching.