Abstract:
:We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pathway-level information, generating a compact and biologically relevant representation of each sample. We demonstrate the algorithm's performance on three colorectal cancer datasets and two glioblastoma multiforme datasets and show that our multipathway-based representation is reproducible, preserves much of the original information, and allows inference of complex biologically significant information. We discovered several pathways that were significantly associated with survival of glioblastoma patients and two whose scores are predictive of survival in colorectal cancer: CXCR3-mediated signaling and oxidative phosphorylation. We also identified a subclass of proneural and neural glioblastoma with significantly better survival, and an EGF receptor-deregulated subclass of colon cancers.
journal_name
Proc Natl Acad Sci U S Aauthors
Drier Y,Sheffer M,Domany Edoi
10.1073/pnas.1219651110subject
Has Abstractpub_date
2013-04-16 00:00:00pages
6388-93issue
16eissn
0027-8424issn
1091-6490pii
1219651110journal_volume
110pub_type
杂志文章abstract::Isolated developing plastids from greening cucumber cotyledons or from photoperiodically grown pea seedlings incorporated (14)C-labeled 5-aminolevulinic acid (ALA) into chlorophyll (Chl). Incorporation was light dependent, enhanced by S-adenosylmethionine, and linear for 1 hr. The in vitro rate of Chl synthesis from A...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.16.5370
更新日期:1985-08-01 00:00:00
abstract::The ability to identify sequences in a randomly encoded polypeptide library that are capable of acquiring unique and stably folded structures would be valuable in the examination of protein-folding issues. The quality control system of the yeast secretory pathway prevents the release of incompletely folded polypeptide...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.102172099
更新日期:2002-05-14 00:00:00
abstract::The development of cardiac hypertrophy is mediated, in part, by increase in NADPH oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in which "phox" is phagocyte oxidase). However, it is not known which Rac isoform ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510444103
更新日期:2006-05-09 00:00:00
abstract::Converging TGF-beta and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.1.460
更新日期:2000-01-04 00:00:00
abstract::During the early evolution of life, 8-oxo-7,8-dihydro-2'-deoxyguanosine (O) may have functioned as a proto-flavin capable of repairing cyclobutane pyrimidine dimers in DNA or RNA by photoinduced electron transfer using longer wavelength UVB radiation. To investigate the ability of O to act as an excited-state electron...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1404411111
更新日期:2014-08-12 00:00:00
abstract::Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy (ICMP) show a reduced neovascularization capacity in vivo. NO plays an important role in neovascularization, and NO bioavailability is typically reduced in patients with ICMP. We investigated whether the impaired neovascularization capacity...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0604144103
更新日期:2006-09-26 00:00:00
abstract::An ADP analog carrying a biotin moiety and a photoreactive group was synthesized. In the presence of vanadate ion (Vi), the analog was tightly trapped into the ATPase site of heavy meromyosin (HMM) or myosin subfragment 1 (S1) in an ADP analog/ATPase site molar ratio of 1:1. UV illumination on the HMM (or S1)-Vi-ADP a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.2.212
更新日期:1986-01-01 00:00:00
abstract::Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0703790104
更新日期:2007-06-12 00:00:00
abstract::The FKBP12-rapamycin-associated protein (FRAP; also called RAFT1/mTOR) regulates translation initiation and entry into the cell cycle. Depriving cells of amino acids or treating them with the small molecule rapamycin inhibits FRAP and results in rapid dephosphorylation and inactivation of the translational regulators ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.8.4438
更新日期:1999-04-13 00:00:00
abstract::MicroRNAs (miRNAs) are small, 18-22 nt long, noncoding RNAs that act as potent negative gene regulators in a variety of physiological and pathological processes. To repress gene expression, miRNAs are packaged into RNA-induced silencing complexes (RISCs) that target mRNAs for degradation and/or translational repressio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1408037111
更新日期:2014-07-01 00:00:00
abstract::We present a model to explain how the neurosecretory system of aquatic mollusks generates their diversity of shell structures and pigmentation patterns. The anatomical and physiological basis of this model sets it apart from other models used to explain shape and pattern. The model reproduces most known shell shapes a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0810311106
更新日期:2009-04-21 00:00:00
abstract::Structural differences between dynein and kinesin suggest a unique molecular mechanism of dynein motility. Measuring the mechanical properties of a single molecule of dynein is crucial for revealing the mechanisms underlying its movement. We measured the step size and force produced by single molecules of active cytop...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0508511103
更新日期:2006-04-11 00:00:00
abstract::X-ray absorption spectra near the Kalpha edge have been measured in various iron group compounds using the intense synchrotron radiation at the Stanford Synchrotron Research Project. In the cubic compounds KMF3 where M = Mn+2, Fe+2, Co+2, Ni+2, and Zn+2, well resolved lines were observed and assigned to the 1s leads t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.5.1384
更新日期:1976-05-01 00:00:00
abstract::Genes encoded by mitochondrial DNA (mtDNA) exist in large numbers per cell but can be selected very rapidly as a result of unequal partitioning of mtDNA between germ cells during embryogenesis. However, empirical studies of this "bottlenecking" effect are rare because of the apparent scarcity of heteroplasmic individu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0802224105
更新日期:2008-04-22 00:00:00
abstract::Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.9.3739
更新日期:1994-04-26 00:00:00
abstract::MicroRNAs (miRNAs) are small RNAs that play a regulatory role in numerous and diverse eukaryotic cellular processes. Virus-encoded miRNAs have garnered much interest, although the functions of most remain to be deciphered. To date, readily detectable, evolutionarily conserved natural miRNAs have only been identified f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1116107109
更新日期:2012-02-21 00:00:00
abstract::Mutations in the DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome; NR0B1] gene cause X-linked AHC associated with hypogonadotropic hypogonadism. DAX-1 encodes an unusual orphan member of the nuclear hormone receptor superfamily, acting as a transcriptional rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.122044099
更新日期:2002-06-11 00:00:00
abstract::Glyoxalase I forms part of the glyoxalase pathway that detoxifies reactive aldehydes such as methylglyoxal, using the spontaneously formed glutathione hemithioacetal as substrate. All known eukaryotic enzymes contain zinc as their metal cofactor, whereas the Escherichia coli glyoxalase I contains nickel. Database mini...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402918101
更新日期:2004-09-07 00:00:00
abstract::The human major histocompatibility complex encodes three classical class I antigens, HLA-A, -B, and -C. Of these HLA-A and -B act as strong transplantation antigens and as restriction molecules for recognition of foreign antigen by cytotoxic T lymphocytes. In contrast, little is known about HLA-C and it is not clear w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.15.5664
更新日期:1988-08-01 00:00:00
abstract::The electrical response of a pigmented lipid bilayer to a short laser pulse is measured by a tunable voltage clamp method. In this method, a variable access impedance permits "tuning" of the observed relaxations for optimal measurements. Analysis of the data so obtained leads to an equivalent circuit that contains a n...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.4.1564
更新日期:1974-04-01 00:00:00
abstract::Development of the vertebrate eye has been found to require the activity of several genes encoding homeodomain proteins (Freund, C., Horsford, D. J. & McInnes, R. R. (1996) Hum. Mol. Genet. 5, 1471-1488). Some of these genes, or portions thereof, are highly conserved across phyla. In this paper, we report the identifi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.7.3088
更新日期:1997-04-01 00:00:00
abstract::Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1532244100
更新日期:2003-07-22 00:00:00
abstract::We have studied the effects of recombinant (r) interleukin 7 (IL-7) on growth and differentiation of marrow pro-B-lymphocyte clones (CB/Bm7, LyD9, LyB9), marrow pro-T-lymphocyte clones (C4-77/3, C4-86/18, C4-95/16), and fetal thymocyte clones (FTH5, FTA2, FTD5) in the presence or absence of the bone marrow stroma clon...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.5.1634
更新日期:1989-03-01 00:00:00
abstract::Point mutations in either of the two nucleotide-binding domains (NBD) of Hsp104 (NBD1 and NBD2) eliminate its thermotolerance function in vivo. In vitro, NBD1 mutations virtually eliminate ATP hydrolysis with little effect on hexamerization; analogous NBD2 mutations reduce ATPase activity and severely impair hexameriz...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.031568098
更新日期:2001-01-30 00:00:00
abstract::Although current theories of color vision differ in many respects, they all assume the existence of a uniquely defined neutral point in chromaticity space. It generally is assumed that this point satisfies several criteria simultaneously. One of these criteria is that it is perceived as achromatic. A further criterion...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.192216699
更新日期:2002-10-01 00:00:00
abstract::Most genetic regulatory mechanisms involve protein-DNA interactions. In these processes, the classical Watson-Crick DNA structure sometimes is distorted severely, which in turn enables the precise recognition of the specific sites by the protein. Despite its key importance, very little is known about such deformation ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.21.12295
更新日期:1998-10-13 00:00:00
abstract::Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms in vivo. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607466103
更新日期:2006-12-12 00:00:00
abstract::Protein 4.1R (4.1R) is a multifunctional component of the red cell membrane. It forms a ternary complex with actin and spectrin, which defines the nodal junctions of the membrane-skeletal network, and its attachment to the transmembrane protein glycophorin C creates a bridge between the protein network and the membran...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803225105
更新日期:2008-06-10 00:00:00
abstract::The photosystem II (PSII) subunit S (PsbS) plays a key role in nonphotochemical quenching, a photoprotective mechanism for dissipation of excess excitation energy in plants. The precise function of PsbS in nonphotochemical quenching is unknown. By reconstituting PsbS together with the major light-harvesting complex of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1205561110
更新日期:2013-04-02 00:00:00
abstract::Characterization and functional annotation of the large number of proteins predicted from genome sequencing projects poses a major scientific challenge. Whereas several proteomics techniques have been developed to quantify the abundance of proteins, these methods provide little information regarding protein function. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501205102
更新日期:2005-04-05 00:00:00