8,535 research outputs found
PseudoFuN: Deriving functional potentials of pseudogenes from integrative relationships with genes and microRNAs across 32 cancers
BACKGROUND:
Long thought "relics" of evolution, not until recently have pseudogenes been of medical interest regarding regulation in cancer. Often, these regulatory roles are a direct by-product of their close sequence homology to protein-coding genes. Novel pseudogene-gene (PGG) functional associations can be identified through the integration of biomedical data, such as sequence homology, functional pathways, gene expression, pseudogene expression, and microRNA expression. However, not all of the information has been integrated, and almost all previous pseudogene studies relied on 1:1 pseudogene-parent gene relationships without leveraging other homologous genes/pseudogenes.
RESULTS:
We produce PGG families that expand beyond the current 1:1 paradigm. First, we construct expansive PGG databases by (i) CUDAlign graphics processing unit (GPU) accelerated local alignment of all pseudogenes to gene families (totaling 1.6 billion individual local alignments and >40,000 GPU hours) and (ii) BLAST-based assignment of pseudogenes to gene families. Second, we create an open-source web application (PseudoFuN [Pseudogene Functional Networks]) to search for integrative functional relationships of sequence homology, microRNA expression, gene expression, pseudogene expression, and gene ontology. We produce four "flavors" of CUDAlign-based databases (>462,000,000 PGG pairwise alignments and 133,770 PGG families) that can be queried and downloaded using PseudoFuN. These databases are consistent with previous 1:1 PGG annotation and also are much more powerful including millions of de novo PGG associations. For example, we find multiple known (e.g., miR-20a-PTEN-PTENP1) and novel (e.g., miR-375-SOX15-PPP4R1L) microRNA-gene-pseudogene associations in prostate cancer. PseudoFuN provides a "one stop shop" for identifying and visualizing thousands of potential regulatory relationships related to pseudogenes in The Cancer Genome Atlas cancers.
CONCLUSIONS:
Thousands of new PGG associations can be explored in the context of microRNA-gene-pseudogene co-expression and differential expression with a simple-to-use online tool by bioinformaticians and oncologists alike
On the exactness of soft theorems
Soft behaviours of S-matrix for massless theories reflect the underlying
symmetry principle that enforces its masslessness. As an expansion in soft
momenta, sub-leading soft theorems can arise either due to (I) unique structure
of the fundamental vertex or (II) presence of enhanced broken-symmetries. While
the former is expected to be modified by infrared or ultraviolet divergences,
the latter should remain exact to all orders in perturbation theory. Using
current algebra, we clarify such distinction for spontaneously broken (super)
Poincar\'e and (super) conformal symmetry. We compute the UV divergences of
DBI, conformal DBI, and A-V theory to verify the exactness of type (II) soft
theorems, while type (I) are shown to be broken and the soft-modifying
higher-dimensional operators are identified. As further evidence for the
exactness of type (II) soft theorems, we consider the alpha' expansion of both
super and bosonic open strings amplitudes, and verify the validity of the
translation symmetry breaking soft-theorems up to O(alpha'^6). Thus the
massless S-matrix of string theory "knows" about the presence of D-branes.Comment: 35 pages. Additional mathematica note book with the UV-divergenece of
the 6-point amplitude in AV/KS theor
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