Derivation of HLA Types from Shotgun Sequence Datasets

The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles directly from shotgun sequence datasets (http://www.bcgsc.ca/platform/bioinfo/software/hlaminer webcite). This approach circumvents the additional time and cost of generating HLA-specific data and capitalizes on the increasing accessibility and affordability of massively parallel sequencing

Network analysis identifies proinflammatory plasma cell polarization for secretion of ISG15 in human autoimmunity

Plasma cells (PCs) as effectors of humoral immunity produce Igs to match pathogenic insult. Emerging data suggest more diverse roles exist for PCs as regulators of immune and inflammatory responses via secretion of factors other than Igs. The extent to which such responses are preprogrammed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. In this study, we dissect the impact of IFNs on the regulatory networks of human PCs. We show that core PC programs are unaffected, whereas PCs respond to IFNs with distinctive transcriptional responses. The IFN-stimulated gene 15 (ISG15) system emerges as a major transcriptional output induced in a sustained fashion by IFN-α in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active systemic lupus erythematosus. Thus, ISG15-secreting PCs represent a distinct proinflammatory PC subset providing an Ig-independent mechanism of PC action in human autoimmunity

The “Narratives” fMRI dataset for evaluating models of naturalistic language comprehension

The “Narratives” collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging

ScreenTrack: Using a Visual History of a Computer Screen to Retrieve Documents and Web Pages

Computers are used for various purposes, so frequent context switching is inevitable. In this setting, retrieving the documents, files, and web pages that have been used for a task can be a challenge. While modern applications provide a history of recent documents for users to resume work, this is not sufficient to retrieve all the digital resources relevant to a given primary document. The histories currently available do not take into account the complex dependencies among resources across applications. To address this problem, we tested the idea of using a visual history of a computer screen to retrieve digital resources within a few days of their use through the development of ScreenTrack. ScreenTrack is software that captures screenshots of a computer at regular intervals. It then generates a time-lapse video from the captured screenshots and lets users retrieve a recently opened document or web page from a screenshot after recognizing the resource by its appearance. A controlled user study found that participants were able to retrieve requested information more quickly with ScreenTrack than under the baseline condition with existing tools. A follow-up study showed that the participants used ScreenTrack to retrieve previously used resources and to recover the context for task resumption.Comment: CHI 2020, 10 pages, 7 figure

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Patterns of edaphic and phenotypic variation in the Lasthenia californica species complex (Asteraceae)

Members of the Lasthenia californica species complex show extensive ecological and phenotypic diversity. This thesis investigates patterns of edaphic, physiological, flavonoid, and morphological differentiation within the Lasthenia californica species complex in two distinct studies. In the first study, patterns of ecological and physiological variation along with flavonoid polymorphism and ITS1 species type distribution were characterized. The hypothesis of parallel evolution of edaphically differentiated flavonoid races across lineages of L. californica sensu lato was also examined in this study. We found evidence refuting the predictions of this hypothesis, particularly that flavonoid type and edaphic environments are correlated across the complex. However, when major axes of ecological and physiological variation were characterized within the complex, the greatest amount of edaphic/tissue variation occurred along lines of toxicity, reaffirming prior characterization. In the second study, the basis of the phenotypic differentiation observed between inland and coastal ecotypes of Lasthenia californica sensu stricto was investigated by growing populations of each ecotype in controlled conditions under varying levels of salinity (an important environmental factor differentiating ecotypic environments). Reaction norms of populations were compared under saline conditions to test for evidence of differential fitness between ecotypes (differential salt tolerance) and differences in intrinsic and induced levels of trait expression (e.g. sodium accumulation and succulence). The hypothesis of trade-offs between salt tolerance and growth potentials was also investigated. Under experimental conditions, coastal populations demonstrated uniformly greater salt tolerance than inland populations. We found that most traits showed both intrinsic differentiation and differential responses to salinity, where the extent and direction of trait responses were ecotype specific with little within ecotype differentiation. When comparing growth rate trends between salt tolerant and non-tolerant populations across salinity treatment levels, we found evidence of trade-offs between maximum intrinsic growth rates and investments in salt tolerance.Science, Faculty ofBotany, Department ofGraduat

Women in Music & Technology

The concert included a PowerPoint presentation on the history of the flute and demonstration of keyboard instruments.Music by women composers; women in music and technology; women in love.Department of Music and Arts Technology; IUPUI Music Academy; IUPUI Asian Pacific American Faculty and Staff Council; IUPUI Office for Women; Piano Solutions for the Roland C-30 "Fortepiano

Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes

Massively parallel sequencing is a useful approach for characterizing T-cell receptor diversity. However, immune receptors are extraordinarily difficult sequencing targets because any given receptor variant may be present in very low abundance and may differ legitimately by only a single nucleotide. We show that the sensitivity of sequence-based repertoire profiling is limited by both sequencing depth and sequencing accuracy. At two timepoints, 1 wk apart, we isolated bulk PBMC plus naïve (CD45RA+/CD45RO−) and memory (CD45RA−/CD45RO+) T-cell subsets from a healthy donor. From T-cell receptor beta chain (TCRB) mRNA we constructed and sequenced multiple libraries to obtain a total of 1.7 billion paired sequence reads. The sequencing error rate was determined empirically and used to inform a high stringency data filtering procedure. The error filtered data yielded 1,061,522 distinct TCRB nucleotide sequences from this subject which establishes a new, directly measured, lower limit on individual T-cell repertoire size and provides a useful reference set of sequences for repertoire analysis. TCRB nucleotide sequences obtained from two additional donors were compared to those from the first donor and revealed limited sharing (up to 1.1%) of nucleotide sequences among donors, but substantially higher sharing (up to 14.2%) of inferred amino acid sequences. For each donor, shared amino acid sequences were encoded by a much larger diversity of nucleotide sequences than were unshared amino acid sequences. We also observed a highly statistically significant association between numbers of shared sequences and shared HLA class I alleles