Decomposition of Gene Expression State Space Trajectories

Representing and analyzing complex networks remains a roadblock to creating dynamic network models of biological processes and pathways. The study of cell fate transitions can reveal much about the transcriptional regulatory programs that underlie these phenotypic changes and give rise to the coordinated patterns in expression changes that we observe. The application of gene expression state space trajectories to capture cell fate transitions at the genome-wide level is one approach currently used in the literature. In this paper, we analyze the gene expression dataset of Huang et al. (2005) which follows the differentiation of promyelocytes into neutrophil-like cells in the presence of inducers dimethyl sulfoxide and all-trans retinoic acid. Huang et al. (2005) build on the work of Kauffman (2004) who raised the attractor hypothesis, stating that cells exist in an expression landscape and their expression trajectories converge towards attractive sites in this landscape. We propose an alternative interpretation that explains this convergent behavior by recognizing that there are two types of processes participating in these cell fate transitions—core processes that include the specific differentiation pathways of promyelocytes to neutrophils, and transient processes that capture those pathways and responses specific to the inducer. Using functional enrichment analyses, specific biological examples and an analysis of the trajectories and their core and transient components we provide a validation of our hypothesis using the Huang et al. (2005) dataset

Characterization of a 105,000 molecular weightgag-related phosphoprotein from cells transformed by the defective avian sarcoma virus PRCII

In cells infected with the replication-defective avian sarcoma virus PRCII a single virus-specific product is detectable, a polyprotein of 105,000 molecular weight (p105). P105 can be precipitated with antisera togag proteins of avian leukosis and sarcoma viruses. By two-dimensional tryptic peptide analysis of [35S]methionine-labeled proteins we have shown that p105 contains peptides of helper viriongag proteins p19 and p27, but not of p15. In addition a number of peptides are present in p105 that are not found in any of the helper virus gene products including gPr95env and Pr180gag-pol. These p105-specific peptides are not detectable in the p60src protein of Rous sarcoma virus (RSV) nor in thegag-related polyproteins encoded by avian myelocytoma and carcinoma viruses MC29 and MH2 or avian erythroblastosis virus AEV. P105 is not detectably glycosylated, but is heavily phosphorylated. In this respect it resembles p60src of RSV rather than the polyproteins of avian leukemia viruses. Since p105 is the only viral gene product detectable in nonproducing cells transformed by PRCII, this protein may be important in the initiation and maintenance of oncogenic transformation. The nonstructural sequences in p105 would then represent a new class of transforming gene in avian oncoviruses

The pathogenicity and defectiveness of PRCII: a new type of avian sarcoma virus

The avian sarcoma virus PRCII (Poultry Research Centre No. 2) transforms fibroblastsin vitro and causes fibromyxosarcomasin vivo. These growths develop after a longer period of latency than Rous sarcomas. PRCII is defective in replication and depends upon an associated helper virus, PRCII AV, for the production of infectious progeny. PRCII AV contains both subgroup A and B envelope determinants. Nonproducer cells transformed in single infection with PRCII do not release viral particles detectable by[3H]uridine incorporation or by reverse transcriptase assay. However, transforming virus can be rescued following super-infection with helper viruses of the chicken leukosis group. Immune precipitation analyses show that PRCII-transformed nonproducer cells do not synthesize the three replicative gene products, Pr76gag, Pr180gag-pol, and gPr95env, but contain a virus-specific protein of 105,000 molecular weight. This PRCII-p105 is precipitable with anti-gag serum, but not with anti-pol serum, anti-env serum, or a broadly reactive anti-src serum. No evidence was found for the expression of p60src in PRCII-transformed cells. PRCII thus represents a new class of avian sarcoma virus distinct from Rous sarcoma virus and its relatives. In the accompanying paper[Neilet al., Virology107, 000 (1980)] we present evidence that PRCII-p105 contains novel sequences not encoded by other transforming oncoviruses

Recovered src genes are polymorphic and contain host markers

Analysis of recovered sarcoma viruses (rASV) and their parental sarcoma virus SR-D by oligonucleotide fingerprinting revealed multiple differences in the src region of the viral genomes. This heterogeneity was further investigated by tryptic peptide mapping of the in vitro translated products of rASV and SR-D RNA. No differences were found in the pr76gag proteins encoded by the various rASVs or SR-D, but the p60src proteins showed considerable variation. The p60src proteins of rASV could be distinguished from that of SR-D on the basis of their mobility in SDS-polyacrylamide gels. Furthermore, two peptides which were absent from SR-D but consistently found in rASV p60src proteins were also demonstrated in a tryptic peptide map of the cellular src-related protein, p60sarc. These results provide strong support for the hypothesis that rASV arose by recombination of residual viral src sequences with cellular src-related sequences

Genetic variation and host markers in the src gene of recovered avian sarcoma viruses

No abstract available