TY - JOUR T1 - Regulation of Lung Endoderm Progenitor Cell Behavior by miR302/367 JF - DevelopmentDevelopmentDevelopmentDevelopment Y1 - 2011 A1 - Tian, Ying A1 - Zhang, Yuzhen A1 - Hurd, Laura A1 - Sridhar Hannenhalli A1 - Liu, Feiyan A1 - Lu, Min Min A1 - Morrisey, Edward E. KW - Lung KW - MicroRNA KW - mouse KW - Progenitor AB - The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity. VL - 138 SN - 0950-1991, 1477-9129 ER - TY - Generic T1 - Inexact Local Alignment Search over Suffix Arrays T2 - IEEE International Conference on Bioinformatics and Biomedicine, 2009. BIBM '09 Y1 - 2009 A1 - Ghodsi, M. A1 - M. Pop KW - bacteria KW - Bioinformatics KW - biology computing KW - Computational Biology KW - Costs KW - DNA KW - DNA homology searches KW - DNA sequences KW - Educational institutions KW - generalized heuristic KW - genes KW - Genetics KW - genome alignment KW - Genomics KW - human KW - inexact local alignment search KW - inexact seeds KW - local alignment KW - local alignment tools KW - memory efficient suffix array KW - microorganisms KW - molecular biophysics KW - mouse KW - Organisms KW - Sensitivity and Specificity KW - sequences KW - suffix array KW - USA Councils AB - We describe an algorithm for finding approximate seeds for DNA homology searches. In contrast to previous algorithms that use exact or spaced seeds, our approximate seeds may contain insertions and deletions. We present a generalized heuristic for finding such seeds efficiently and prove that the heuristic does not affect sensitivity. We show how to adapt this algorithm to work over the memory efficient suffix array with provably minimal overhead in running time. We demonstrate the effectiveness of our algorithm on two tasks: whole genome alignment of bacteria and alignment of the DNA sequences of 177 genes that are orthologous in human and mouse. We show our algorithm achieves better sensitivity and uses less memory than other commonly used local alignment tools. JA - IEEE International Conference on Bioinformatics and Biomedicine, 2009. BIBM '09 PB - IEEE SN - 978-0-7695-3885-3 ER -