排序方式: 共有107条查询结果,搜索用时 644 毫秒
1.
Roy Ronen Glenn Tesler Ali Akbari Shay Zakov Noah A. Rosenberg Vineet Bafna 《PLoS genetics》2015,11(9)
Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations. 相似文献
2.
The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds. 相似文献
3.
Sangwoo Kim Kyowon Jeong Kunal Bhutani Jeong Ho Lee Anand Patel Eric Scott Hojung Nam Hayan Lee Joseph G Gleeson Vineet Bafna 《Genome biology》2013,14(8):R90
Detection of somatic variation using sequence from disease-control matched data sets is a critical first step. In many cases including cancer, however, it is hard to isolate pure disease tissue, and the impurity hinders accurate mutation analysis by disrupting overall allele frequencies. Here, we propose a new method, Virmid, that explicitly determines the level of impurity in the sample, and uses it for improved detection of somatic variation. Extensive tests on simulated and real sequencing data from breast cancer and hemimegalencephaly demonstrate the power of our model. A software implementation of our method is available at http://sourceforge.net/projects/virmid/. 相似文献
4.
Genomic sequence duplication is an important mechanism for genome evolution, often resulting in large sequence variations with implications for disease progression. Although paired-end sequencing technologies are commonly used for structural variation discovery, the discovery of novel duplicated sequences remains an unmet challenge. We analyze duplicons starting from identified high-copy number variants. Given paired-end mapped reads, and a candidate high-copy region, our tool, Reprever, identifies (a) the insertion breakpoints where the extra duplicons inserted into the donor genome and (b) the actual sequence of the duplicon. Reprever resolves ambiguous mapping signatures from existing homologs, repetitive elements and sequencing errors to identify breakpoint. At each breakpoint, Reprever reconstructs the inserted sequence using profile hidden Markov model (PHMM)-based guided assembly. In a test on 1000 artificial genomes with simulated duplication, Reprever could identify novel duplicates up to 97% of genomes within 3 bp positional and 1% sequence errors. Validation on 680 fosmid sequences identified and reconstructed eight duplicated sequences with high accuracy. We applied Reprever to reanalyzing a re-sequenced data set from the African individual NA18507 to identify >800 novel duplicates, including insertions in genes and insertions with additional variation. polymerase chain reaction followed by capillary sequencing validated both the insertion locations of the strongest predictions and their predicted sequence. 相似文献
5.
目的:探讨280例胃食管反流病(GERD)的分布特点及危险因素。方法:对临床诊断和胃镜确诊的280例GERD患者进行临床和风险因子相关性分析。结果:不论汉族还是维族,男性患者比例均明显高于女性;汉族患者高发年龄段早于维族患者(z=-2.939,P=0.003,);汉族和维族患者占反流性食管炎和Barrett食管比例分别为42.4%、81_3%及56.5%、18.8%,其中汉族患者Barrett食管比例较高(X2=14.358,P=0.000);肥胖、习惯性便秘、重体力活动者、饮食习惯不良在维族患者中的比例较高(P〈0.001)。结论:GERD与性别、年龄密切相关,男性多于女性,汉族患者发病年龄高峰旱于维族患者;汉族患者Barrett食管发生比例高于维族患者;肥胖、习惯性便秘、重体力活动、饮食习惯不良可能是GERD尤其是维族人群GERD的危险因素。 相似文献
6.
Vinaya Kumar Golla Eulàlia Sans-Serramitjana Karunakar Reddy Pothula Lorraine Benier Jayesh Arun Bafna Mathias Winterhalter Ulrich Kleinekathöfer 《Biophysical journal》2019,116(2):258-269
Fosfomycin is a frequently prescribed drug in the treatment of acute urinary tract infections. It enters the bacterial cytoplasm and inhibits the biosynthesis of peptidoglycans by targeting the MurA enzyme. Despite extensive pharmacological studies and clinical use, the permeability of fosfomycin across the bacterial outer membrane is largely unexplored. Here, we investigate the fosfomycin permeability across the outer membrane of Gram-negative bacteria by electrophysiology experiments as well as by all-atom molecular dynamics simulations including free-energy and applied-field techniques. Notably, in an electrophysiological zero-current assay as well as in the molecular simulations, we found that fosfomycin can rapidly permeate the abundant Escherichia coli porin OmpF. Furthermore, two triple mutants in the constriction region of the porin have been investigated. The permeation rates through these mutants are slightly lower than that of the wild type but fosfomycin can still permeate. Altogether, this work unravels molecular details of fosfomycin permeation through the outer membrane porin OmpF of E. coli and moreover provides hints for understanding the translocation of phosphonic acid antibiotics through other outer membrane pores. 相似文献
7.
Jolanda?HM?van Bilsen Josée?PA?Wagenaar-Hilbers Maarten?JF?van der Cammen Mariska?EA?van Dijk Willem?van Eden Marca?HM?WaubenEmail author 《Arthritis research & therapy》2002,4(4):R2
We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental
arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the
course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration
of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the
MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP
peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development
of such therapies. 相似文献
8.
Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis 总被引:1,自引:0,他引:1
Group B and C Neisseria meningitidis are the major cause of meningococcal
disease in the United States and in Europe. N . meningitidis
lipooligosaccharide (LOS), a major surface antigen, can be divided into 12
immunotypes of which L1 through L8 were found among Group B and C
organisms. Groups B and C but not Group A may sialylate their LOSs with
N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they
synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as
probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4,
L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis
leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc
sequence, but not to Sambucus nigra agglutinin, which binds
NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot
analyses revealed that these six LOSs contained only the
NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS
components, which have a common terminal lacto-N-neotetraose (LNnT,
Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown
by previous studies. The LOS-lectin binding was abolished when the LOSs
were treated with Newcastle disease viral neuraminidase which cleaves
alpha2-->3 linked sialic acid. Methylation analysis of a representative
LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs
structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide)
and sialylparagloboside and some glycoproteins in having LNnT and
N-acetyllactosamine sequences, respectively, with or without alpha2-->3
linked NeuNAc. The molecular mimicry of the LOSs may play a role in the
pathogenesis of N.meningitidis by assisting the organism to evade host
immune defenses in man.
相似文献
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We investigated the role of the main olfactory and accessory olfactory systems (MOS and AOS respectively) in the detection of androstenone. We used the following experimental approaches: behavioral, surgical removal of the vomeronasal organ (VNX) followed by histochemical verification and Fos immunohistochemistry. Using a Y-maze paradigm we estimated sensitivity of NZB/B1NJ and CBA/J mice to androstenone. CBA mice were 2,000-fold more sensitive to androstenone than NZB mice. VNX caused a 4- to 16-fold decre... 相似文献