Highlights from the Third International Society for Computational Biology Student Council Symposium at the Fifteenth Annual International Conference on Intelligent Systems for Molecular Biology

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract In this meeting report we give an overview of the 3rd International Society for Computational Biology Student Council Symposium. Furthermore, we explain the role of the Student Council and the symposium series in the context of large, international conferences.Published versio

Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions

Improvements in sequencing technologies and reduced experimental costs have resulted in a vast number of studies generating high-throughput data. Although the number of methods to analyze these "omics" data has also increased, computational complexity and lack of documentation hinder researchers from analyzing their high-throughput data to its true potential. In this chapter we detail our data-driven, transkingdom network (TransNet) analysis protocol to integrate and interrogate multi-omics data. This systems biology approach has allowed us to successfully identify important causal relationships between different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of data

Understanding Visualization Authoring Techniques for Genomics Data in the Context of Personas and Tasks

Genomics experts rely on visualization to extract and share insights from complex and large-scale datasets. Beyond off-the-shelf tools for data exploration, there is an increasing need for platforms that aid experts in authoring customized visualizations for both exploration and communication of insights. A variety of interactive techniques have been proposed for authoring data visualizations, such as template editing, shelf configuration, natural language input, and code editors. However, it remains unclear how genomics experts create visualizations and which techniques best support their visualization tasks and needs. To address this gap, we conducted two user studies with genomics researchers: (1) semi-structured interviews (n = 20) to identify the tasks, user contexts, and current visualization authoring techniques and (2) an exploratory study (n = 13) using visual probes to elicit users' intents and desired techniques when creating visualizations. Our contributions include (1) a characterization of how visualization authoring is currently utilized in genomics visualization, identifying limitations and benefits in light of common criteria for authoring tools, and (2) generalizable design implications for genomics visualization authoring tools based on our findings on task- and user-specific usefulness of authoring techniques. All supplemental materials are available at https://osf.io/bdj4v/.</p

Learnable and Expressive Visualization Authoring through Blended Interfaces

A wide range of visualization authoring interfaces enable the creation of highly customized visualizations. However, prioritizing expressiveness often impedes the learnability of the authoring interface. The diversity of users, such as varying computational skills and prior experiences in user interfaces, makes it even more challenging for a single authoring interface to satisfy the needs of a broad audience. In this paper, we introduce a framework to balance learnability and expressivity in a visualization authoring system. Adopting insights from learnability studies, such as multimodal interaction and visualization literacy, we explore the design space of blending multiple visualization authoring interfaces for supporting authoring tasks in a complementary and flexible manner. To evaluate the effectiveness of blending interfaces, we implemented a proof-of-concept system, Blace, that combines four common visualization authoring interfaces-template-based, shelf configuration, natural language, and code editor-that are tightly linked to one another to help users easily relate unfamiliar interfaces to more familiar ones. Using the system, we conducted a user study with 12 domain experts who regularly visualize genomics data as part of their analysis workflow. Participants with varied visualization and programming backgrounds were able to successfully reproduce unfamiliar visualization examples without a guided tutorial in the study. Feedback from a post-study qualitative questionnaire further suggests that blending interfaces enabled participants to learn the system easily and assisted them in confidently editing unfamiliar visualization grammar in the code editor, enabling expressive customization. Reflecting on our study results and the design of our system, we discuss the different interaction patterns that we identified and design implications for blending visualization authoring interfaces.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment