The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

/pdf/gapped-blast-and-psi-blast-a-new-generation-of-protein-2ybl67x5yx.pdf

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

/pdf/identification-and-analysis-of-functional-elements-in-1-of-2o640l8ikl.pdf

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Matrix metalloproteinases (MMPs), also designated matrixins, hydrolyze components of the extracellular matrix. These proteinases play a central role in many biological processes, such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. Currently 23 MMP genes have been identified in humans, and most are multidomain proteins. This review describes the members of the matrixin family and discusses substrate specificity, domain structure and function, the activation of proMMPs, the regulation of matrixin activity by tissue inhibitors of metalloproteinases, and their pathophysiological implication.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.

Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules

Genome evolution and the evolution of exon-shuffling--a review.

Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2887%2980002-9

László Patthy

Papers

Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules

Genome evolution and the evolution of exon-shuffling--a review.

Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues.

Intron-dependent evolution: preferred types of exons and introns.

The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator.