383 research outputs found
MIMOX: a web tool for phage display based epitope mapping
BACKGROUND: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at
Viral integration drives multifocal HCC during the occult HBV infection
© 2019 The Author(s). Background & Aims: Although the prognosis of patients with occult hepatitis B virus (HBV) infection (OBI) is usually benign, a small portion may undergo cirrhosis and subsequently hepatocellular carcinoma (HCC). We studied the mechanism of life-long Integration of virus DNA into OBI host's genome, of which may induce hepatocyte transformation. Methods: We applied HBV capture sequencing on single cells from an OBI patient who, developed multiple HCC tumors and underwent liver resection in May 2013 at Tongji Hospital in China. Despite with the undetectable virus DNA in serum, we determined the pattern of viral integration in tumor cells and adjacent non-tumor cells and obtained the details of the viral arrangement in host genome, and furthermore the HBV integrated region in cancer genome. Results: HBV captured sequencing of tissues and individual cells revealed that samples from multiple tumors shared two viral integration sites that could affect three host genes, including CSMD2 on chr1 and MED30/EXT1 on chr8. Whole genome sequencing further indicated one hybrid chromosome formed by HBV integrations between chr1 and chr8 that was shared by multiple tumors. Additional 50 poorly differentiated liver tumors and the paired adjacent non-tumors were evaluated and functional studies suggested up-regulated EXT1 expression promoted HCC growth. We further observed that the most somatic mutations within the tumor cell genome were common among the multiple tumors, suggesting that HBV associated, multifocal HCC is monoclonal in origin. Conclusion: Through analyzing the HBV integration sites in multifocal HCC, our data suggested that the tumor cells were monoclonal in origin and formed in the absence of active viral replication, whereas the affected host genes may subsequently contribute to carcinogenesis
Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon
Using data collected by the CLEO detector in the Upsilon(4S) region, we
report new measurements of the exclusive decays of B mesons into final states
of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes
with one, two and three pions and an upper limit for the two body decay
Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B
mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one
and two pions and an upper limit for the two body decay Sigma_c p-bar.
Measurements of these modes shed light on the mechanisms involved in B decays
to baryons.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons
Using data recorded by the CLEO II and CLEO II.V detector configurations at
CESR, we report new measurements of the masses of the Sigma_c^{++} and
Sigma_c^0 charmed baryons, and the first measurements of their intrinsic
widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV,
Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) =
167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the
uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid
Communications. Reference [13] correcte
A Gene's Ability to Buffer Variation Is Predicted by Its Fitness Contribution and Genetic Interactions
BACKGROUND: Many single-gene knockouts result in increased phenotypic (e.g., morphological) variability among the mutant's offspring. This has been interpreted as an intrinsic ability of genes to buffer genetic and environmental variation. A phenotypic capacitor is a gene that appears to mask phenotypic variation: when knocked out, the offspring shows more variability than the wild type. Theory predicts that this phenotypic potential should be correlated with a gene's knockout fitness and its number of negative genetic interactions. Based on experimentally measured phenotypic capacity, it was suggested that knockout fitness was unimportant, but that phenotypic capacitors tend to be hubs in genetic and physical interaction networks. METHODOLOGY/PRINCIPAL FINDINGS: We re-analyse the available experimental data in a combined model, which includes knockout fitness and network parameters as well as expression level and protein length as predictors of phenotypic potential. Contrary to previous conclusions, we find that the strongest predictor is in fact haploid knockout fitness (responsible for 9% of the variation in phenotypic potential), with an additional contribution from the genetic interaction network (5%); once these two factors are taken into account, protein-protein interactions do not make any additional contribution to the variation in phenotypic potential. CONCLUSIONS/SIGNIFICANCE: We conclude that phenotypic potential is not a mysterious "emergent" property of cellular networks. Instead, it is very simply determined by the overall fitness reduction of the organism (which in its compromised state can no longer compensate for multiple factors that contribute to phenotypic variation), and by the number (and presumably nature) of genetic interactions of the knocked-out gene. In this light, Hsp90, the prototypical phenotypic capacitor, may not be representative: typical phenotypic capacitors are not direct "buffers" of variation, but are simply genes encoding central cellular functions
Evidence for the Decay
We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9
fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay
can occur either through a doubly Cabibbo-suppressed process or through mixing
to a D0bar followed by a Cabibbo-favored process. Our result for the
time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is
(0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space),
which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays
We have measured the first and second moments of the hadronic mass-squared
distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 -
M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170
GeV^4, where M_D[Bar] is the spin-averaged D meson mass.
From that first moment and the first moment of the photon energy spectrum in
b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and
beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the
B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| =
0.0404 +- 0.0013.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Observation of Exclusive barB --> D(*) K*- Decays
We report the first observation of the exclusive decays \bar B\to
D^{(*)}K^{*-}, using 9.66 x 10^{6} B\bar{B} pairs collected at the \Upsilon(4S)
with the CLEO detector. We measure the following branching fractions: {\cal
B}(B^- -> D^0 K^{*-})=(6.1 +- 1.6 +-1.7)x10^{-4}, {\cal B}(\bar{B^0} ->
D^+K^{*-})=(3.7 +- 1.5 +- 1.0) x 10^{-4}, {\cal B}(\bar{B^0} ->
D^{*+}K^{*-})=(3.8 +- 1.3 +- 0.8) x 10^{-4} and {\cal B}(B^- --> D^{*0}
K^{*-})=(7.7 +- 2.2 +- 2.6) x 10^{-4}. The \bar B ->D^*K^{*-} branching ratios
are the averages of those corresponding to the 00 and 11 helicity states. The
errors shown are statistical and systematic, respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, Published in
Phys.Rev.Lett.88:101803,200
Observation of the Charmed Baryon at CLEO
The CLEO experiment at the CESR collider has used 13.7 fb of data to
search for the production of the (css-ground state) in
collisions at {\rm GeV}. The modes used to
study the are ,
, , , and
. We observe a signal of 40.49.0(stat) events
at a mass of 2694.62.6(stat)1.9(syst) {\rm MeV/}, for all modes
combined.Comment: 10 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Observation of and
We have studied two-body charmless hadronic decays of mesons into the
final states phi K and phi K^*. Using 9.7 million pairs collected
with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0
with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6)
x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see
evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the
statistical significance is not overwhelming for these modes we determine upper
limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
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