Assigning functions to proteins of unknown function is of considerable interest to the proteomic researchers as the genes encoding them are conserved over
various species. Here, we describe HypoDB, a database of hypothetical genes and proteins in six eukaryotes. The database was collected and organized based on
the number of entries in each chromosome with few annotations. Hypothetical protein database contains information related to gene and protein sequences,
chromosome number and location, secondary and tertiary structure related data.AvailabilityThe database is available for free at
http://www.trimslabs.com/database/hypodb/index.html
Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions, though largely as a retrospective tool. Prospective monitoring, in which samples are continuously added and compared to previous samples, can generate more actionable information. To enable prospective pathogen comparison, genomic relatedness metrics based on single-nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare,
i.e
., the
core genome
, is critical to obtain a good metric. We propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436
S. aureus
, 1362
K. pneumoniae
and 348
E. faecium
samples, ROC curves demonstrate that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high sensitivity: in a set of 2335
S. aureus
samples, it correctly identifies 44 out of 44 known outbreak samples, whereas the conserved-gene method confirms 38 known outbreak samples.
The recent advances in immune checkpoint (IC) blockade highlight the need to develop novel IC drug combinations. However, it remains challenging to determine which IC should be targeted in a particular indication. Enumeral uses an innovative approach to identify relevant ICs for which blockade could restore immune cell function. We use our proprietary single cell technology to assess the tumor microenvironment of human tissues and to elucidate the appropriate IC to antagonize on tumor infiltrating lymphocytes. Once appropriate IC targets are found in human tumors, monoclonal antibodies are generated and validated in vitro and ex-vivo. We tested combinations of monoclonal antibodies against ICs at the single cell level in tumor samples for reversal of immune cell exhaustion. Several anti-PD-1 and anti-TIM-3 lead candidates have been characterized in preparation for clinical studies using this strategy.
Citation Format: Thomas McQuade, Yanyan Wang, Daniel Doty, Najmia Amirina, Sri Vadde, Hareesh Chamarthi, Cokey Nguyen, Sheila Ranganath, Jennifer Watkins-Yoon. Human tumor-based identification of immune checkpoint targets. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B083.
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