Tackling Big Genomics Data

Presented at Internet 2 Global Summit, Denver, CO. 7 April 2014This material is based upon work supported by the National Science Foundation under Grant No. ABI-1062432, Craig Stewart, PI. William Barnett, Matthew Hahn, and Michael Lynch, co-PIs. This work was supported in part by the Lilly Endowment, Inc. and the Indiana University Pervasive Technology Institute. Any opinions presented here are those of the presenter(s) and do not necessarily represent the opinions of the National Science Foundation or any other funding agencie

Careers in Computing and Science

This material is based upon work supported by the National Science Foundation under Grants No. ABI-1062432 Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation

Optimizing the National Cyberinfrastructure for Lower Bioinformatic Costs: Making the Most of Resources for Publicly Funded Research

Presented at the RNA-Seq Conference, June 18-20, 2013 in Boston MassachusettsOverviews of NCGAS mission, cyberinfrastructure, and server-on-demand resources and of XSEDE for larger-scale resources.This material is based upon work supported by the National Science Foundation under Grants No. ABI-1062432. This work was supported in part by the Lilly Endowment, Inc. and the Indiana University Pervasive Technology Institute Any opinions presented here are those of the presenter(s) and do not necessarily represent the opinions of the National Science Foundation or any other funding agencie

Synthèses d'acides aminés à haute lipophilicite et leur introduction dans l'angiotensine II

L'adamantylalanine, un composé faisant partie d'une nouvelle famille d'acides aminés et possédant des propriétés physicochimiques intéressantes, a été synthétisée de façon asymétrique. Son incorporation dans l'angiotensine II (AT) à la position 8 a montré un effet antagoniste. La synthèse du l',2',3',4',5'-pentabromo-phénylalanine, (Br5-Phe), est assez difficile à réaliser à cause d'important facteurs stériques venant du noyau phényl perbromé (5 atomes de brome). Plusieurs chemins de synthèses ont été tentés et on a pu finalement Ïsoler des quantités significatives de ce nouvel acide aminé. Certaines vérifications (RMN, analyse élémentaire, CCM) ont confirmé sa structure. [...

National Center for Genome Analysis Program Year 2 Report – September 15, 2012 – September 14, 2013

On September 15, 2011, Indiana University (IU) received three years of support to establish the National Center for Genome Analysis Support (NCGAS). This technical report describes the activities of the second 12 months of NCGASThe facilities supported by the Research Technologies division at Indiana University are supported by a number of grants. The authors would like to acknowledge that although the National Center for Genome Analysis Support is funded by NSF 1062432, our work would not be possible without the generous support of the following awards received by our parent organization, the Pervasive Technology Institute at Indiana University. • The Indiana University Pervasive Technology Institute was supported in part by two grants from the Lilly Endowment, Inc. • NCGAS has also been supported directly by the Indiana METACyt Initiative. The Indiana METACyt Initiative of Indiana University is supported in part by the Lilly Endowment, Inc. • This material is based in part upon work supported by the National Science Foundation under Grant No. CNS-0521433. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation (NSF)

ESTIMA, a tool for EST management in a multi-project environment

BACKGROUND: Single-pass, partial sequencing of complementary DNA (cDNA) libraries generates thousands of chromatograms that are processed into high quality expressed sequence tags (ESTs), and then assembled into contigs representative of putative genes. Usually, to be of value, ESTs and contigs must be associated with meaningful annotations, and made available to end-users. RESULTS: A web application, Expressed Sequence Tag Information Management and Annotation (ESTIMA), has been created to meet the EST annotation and data management requirements of multiple high-throughput EST sequencing projects. It is anchored on individual ESTs and organized around different properties of ESTs including chromatograms, base-calling quality scores, structure of assembled transcripts, and multiple sources of comparison to infer functional annotation, Gene Ontology associations, and cDNA library information. ESTIMA consists of a relational database schema and a set of interactive query interfaces. These are integrated with a suite of web-based tools that allow a user to query and retrieve information. Further, query results are interconnected among the various EST properties. ESTIMA has several unique features. Users may run their own EST processing pipeline, search against preferred reference genomes, and use any clustering and assembly algorithm. The ESTIMA database schema is very flexible and accepts output from any EST processing and assembly pipeline. ESTIMA has been used for the management of EST projects of many species, including honeybee (Apis mellifera), cattle (Bos taurus), songbird (Taeniopygia guttata), corn rootworm (Diabrotica vergifera), catfish (Ictalurus punctatus, Ictalurus furcatus), and apple (Malus x domestica). The entire resource may be downloaded and used as is, or readily adapted to fit the unique needs of other cDNA sequencing projects. CONCLUSIONS: The scripts used to create the ESTIMA interface are freely available to academic users in an archived format from . The entity-relationship (E-R) diagrams and the programs used to generate the Oracle database tables are also available. We have also provided detailed installation instructions and a tutorial at the same website. Presently the chromatograms, EST databases and their annotations have been made available for cattle and honeybee brain EST projects. Non-academic users need to contact the W.M. Keck Center for Functional and Comparative Genomics, University of Illinois at Urbana-Champaign, Urbana, IL, for licensing information

Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling.

Matriptase is an epithelia-specific membrane-anchored serine protease that has received considerable attention in recent years because of its consistent dysregulation in human epithelial tumours, including breast cancer. Mice with reduced levels of matriptase display a significant delay in oncogene-induced mammary tumour formation and blunted tumour growth. The abated tumour growth is associated with a decrease in cancer cell proliferation. Here we demonstrate by genetic deletion and silencing that the proliferation impairment in matriptase-deficient breast cancer cells is caused by their inability to initiate activation of the c-Met signalling pathway in response to fibroblast-secreted pro-HGF. Similarly, inhibition of matriptase catalytic activity using a selective small-molecule inhibitor abrogates the activation of c-Met, Gab1 and AKT, in response to pro-HGF, which functionally leads to attenuated proliferation in breast carcinoma cells. We conclude that matriptase is critically involved in breast cancer progression and represents a potential therapeutic target in breast cancer

Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer.

The poor prognosis for patients with inflammatory breast cancer (IBC) compared to patients with other types of breast cancers emphasizes the need to better understand the molecular underpinnings of this disease with the goal of developing effective targeted therapeutics. Dysregulation of matriptase expression, an epithelial-specific member of the type II transmembrane serine protease family, has been demonstrated in many different cancer types. To date, no studies have assessed the expression and potential pro-oncogenic role of matriptase in IBC. We examined the functional relationship between matriptase and the HGF/c-MET signaling pathway in the IBC cell lines SUM149 and SUM190, and in IBC patient samples. Matriptase and c-Met proteins are localized on the surface membrane of IBC cells and their expression is strongly correlated in infiltrating cancer cells and in the cancer cells of lymphatic emboli in patient samples. Abrogation of matriptase expression by silencing with RNAi or inhibition of matriptase proteolytic activity with a synthetic inhibitor impairs the conversion of inactive pro-HGF to active HGF and subsequent c-Met-mediated signaling, leading to efficient impairment of proliferation and invasion of IBC cells. These data show the potential of matriptase inhibitors as a novel targeted therapy for IBC, and lay the groundwork for the development and testing of such drugs