PISCES: recent improvements to a PDB sequence culling server

PISCES is a database server for producing lists of sequences from the Protein Data Bank (PDB) using a number of entry- and chain-specific criteria and mutual sequence identity. Our goal in culling the PDB is to provide the longest list possible of the highest resolution structures that fulfill the sequence identity and structural quality cut-offs. The new PISCES server uses a combination of PSI-BLAST and structure-based alignments to determine sequence identities. Structure alignment produces more complete alignments and therefore more accurate sequence identities than PSI-BLAST. PISCES now allows a user to cull the PDB by-entry in addition to the standard culling by individual chains. In this scenario, a list will contain only entries that do not have a chain that has a sequence identity to any chain in any other entry in the list over the sequence identity cut-off. PISCES also provides fully annotated sequences including gene name and species. The server allows a user to cull an input list of entries or chains, so that other criteria, such as function, can be used. Results from a search on the re-engineered RCSB's site for the PDB can be entered into the PISCES server by a single click, combining the powerful searching abilities of the PDB with PISCES's utilities for sequence culling. The server's data are updated weekly. The server is available at

A unified approach to non-negative matrix factorization and probabilistic latent semantic indexing

Non-negative matrix factorization (NMF) by the multiplicative updates algorithm is a powerful machine learning method for decomposing a high-dimensional nonnegative matrix V into two matrices, W and H, each with nonnegative entries, V ~ WH. NMF has been shown to have a unique parts-based, sparse representation of the data. The nonnegativity constraints in NMF allow only additive combinations of the data which enables it to learn parts that have distinct physical representations in reality. In the last few years, NMF has been successfully applied in a variety of areas such as natural language processing, information retrieval, image processing, speech recognition and computational biology for the analysis and interpretation of large-scale data. We present a generalized approach to NMF based on Renyi\u27s divergence between two non-negative matrices related to the Poisson likelihood. Our approach unifies various competing models and provides a unique framework for NMF. Furthermore, we generalize the equivalence between NMF and probabilistic latent semantic indexing, a well-known method used in text mining and document clustering applications. We evaluate the performance of our method in the unsupervised setting using consensus clustering and demonstrate its applicability using real-life and simulated data

Nrf2 Deficiency Augments the Activity of Hepatic Progenitor Cells during Cholestasis

poster abstractTranscription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular defense against oxidative stress and inflammation and is also involved in regulating liver regeneration. The aim of the study is to evaluate whether Nrf2 mediates hepatic repair response during cholestasis. Wild-type and Nrf2-null mice were subjected to bile duct ligation or sham operation. Various assessments were performed at 5, 10, 15, 25, and 40 days following surgery. Significant genotype-dependent differences in liver injury, cell proliferation, and collagen deposition were not seen over the time course of the study, in line with several reports. However, Nrf2-null mice exhibited a more prominent network of septual tissue containing laminin and α-fetal protein expressing cells at 15 days after injury, suggesting a stronger repair response, than their wild-type litter mates. In the livers of both genotypes of mice, cytokeratin 19 (CK19), a marker of bipotent liver epithelial progenitors and immature billiary epithelial cells, were expressed in the epithelial cells of newly formed bile ducts and a population of hepatocytic-appearing cells in parenchyma. Notably, Nrf2-null mice showed higher hepatic protein expression of CK19 at 5 days following BDL, indicating earlier onset of the activation of CK19+ progenitor cells, than wild-types. CD133, a marker of liver progenitors, were found to be expressed by newly generated bile duct epithelial cells and a population of hepatocytic-appearing parenchymal cells in the livers of the two genotypes of mice. Hepatic CD133 protein expression was gradually elevated, paralleling continuous increase in the number of CD133+ hepatocytic-appearing cells, as the cholestasis progressed. Remarkably, the lack of Nrf2 led to markedly higher magnitudes of the increases in hepatic CD133 protein level and in the number of CD133+ hepatocytic-appearing cells. Collectively, our data demonstrate that Nrf2 deficiency evokes higher activity of liver progenitor cells and thus stronger liver repair response. The findings indicate that Nrf2 is an important regulator of the activity of hepatic progenitor/stem cells during chronic liver injury