Howard Hughes Medical Institute

About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.

Abnormalities in Structure and Expression of the Human Retinoblastoma Gene in SCLC

Abstract: Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene (Rb) localized at 13q14, might be the target of recessive mutations in lung cancer, eight primary SCLC tumors and 50 cell lines representing all major histologic types of lung cancer were examined with the Rb complementary DNA probe. Structural abnormalities within the Rb gene were observed in 1/8 (13%) primary SCLC tumors, 4/22 (18%) SCLC lines, and 1/4 (25%) pulmonary carcinoid lines (comparable to the 20 to 40% observed in retinoblastoma), but were not detected in other major types of lung cancer. Rb messenger RNA expression was absent in 60% of the SCLC lines and 75% of pulmonary carcinoid lines, including all samples with DNA abnormalities. In contrast, Rb transcripts were found in 90% of non-SCLC lung cancer lines and in normal human lung. The finding of abnormalities of the Rb gene in SCLC and pulmonary carcinoids (both neuroendocrine tumors) suggests that this gene may be involved in the pathogenesis of a common adult malignancy.

Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1

Abstract: Cells of the monocyte-macrophage lineage are targets for human immunodeficiency virus-1 (HIV-1) infection in vivo. However, many laboratory strains of HIV-1 that efficiently infect transformed T cell lines replicate poorly in macrophages. A 20-amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confer macrophage tropism on HTLV-IIIB, a T cell line--tropic isolate. This small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV-1. Thus, the V3 loop not only serves as a target of the host immune response but is also pivotal in determining HIV-1 tissue tropism.

Hidden Markov model speed heuristic and iterative HMM search procedure

Abstract: Profile hidden Markov models (profile-HMMs) are sensitive tools for remote protein homology detection, but the main scoring algorithms, Viterbi or Forward, require considerable time to search large sequence databases. We have designed a series of database filtering steps, HMMERHEAD, that are applied prior to the scoring algorithms, as implemented in the HMMER package, in an effort to reduce search time. Using this heuristic, we obtain a 20-fold decrease in Forward and a 6-fold decrease in Viterbi search time with a minimal loss in sensitivity relative to the unfiltered approaches. We then implemented an iterative profile-HMM search method, JackHMMER, which employs the HMMERHEAD heuristic. Due to our search heuristic, we eliminated the subdatabase creation that is common in current iterative profile-HMM approaches. On our benchmark, JackHMMER detects 14% more remote protein homologs than SAM's iterative method T2K. Our search heuristic, HMMERHEAD, significantly reduces the time needed to score a profile-HMM against large sequence databases. This search heuristic allowed us to implement an iterative profile-HMM search method, JackHMMER, which detects significantly more remote protein homologs than SAM's T2K and NCBI's PSI-BLAST.