Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Zhen Chen, Yongzi Chen, Xiao Feng Wang et al. · 2011 · PLoS ONE
As one of the most important reversible protein post-translation modifications, ubiquitination has been reported to be involved in lots of biological processes and closely implicated with various diseases. To fully decipher the molecular mechanisms of ubiquitination-related biological processes, an initial but crucial step is the recognition of ubiquitylated substrates and the corresponding ubiquitination sites. Here, a new bioinformatics tool named CKSAAP_UbSite was developed to predict ubiquitination sites from protein sequences. With the assistance of Support Vector Machine (SVM), the highl
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Brendan O’Fallon, Lars Fehren‐Schmitz · 2011 · Proceedings of the National Academy of Sciences
The genetic and demographic impact of European contact with Native Americans has remained unclear despite recent interest. Whereas archeological and historical records indicate that European contact resulted in widespread mortality from…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Florian Gnad, Albion Baucom, Kiran Mukhyala et al. · 2013 · BMC Genomics
BACKGROUND: Recent advances in sequencing technologies have greatly increased the identification of mutations in cancer genomes. However, it remains a significant challenge to identify cancer-driving mutations, since most observed missense changes are neutral passenger mutations. Various computational methods have been developed to predict the effects of amino acid substitutions on protein function and classify mutations as deleterious or benign. These include approaches that rely on evolutionary conservation, structural constraints, or physicochemical attributes of amino acid substitutions. H
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Federico Innocenti, Gregory M. Cooper, Ian B. Stanaway et al. · 2011 · PLoS Genetics
The discovery of expression quantitative trait loci ("eQTLs") can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Kieu Trinh, Simone Wahl, Johannes Raffler et al. · 2018 · Metabolomics
BACKGROUND: Untargeted mass spectrometry (MS)-based metabolomics data often contain missing values that reduce statistical power and can introduce bias in biomedical studies. However, a systematic assessment of the various sources of missing values and strategies to handle these data has received little attention. Missing data can occur systematically, e.g. from run day-dependent effects due to limits of detection (LOD); or it can be random as, for instance, a consequence of sample preparation. METHODS: We investigated patterns of missing data in an MS-based metabolomics experiment of serum sa
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Jack Kuipers, Katharina Jahn, Benjamin J. Raphael et al. · 2017 · Genome Research
Intra-tumor heterogeneity poses substantial challenges for cancer treatment. A tumor's composition can be deduced by reconstructing its mutational history. Central to current approaches is the infinite sites assumption that every genomic…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Daniel E. Bonder, Ken D. McCarthy · 2014 · Journal of Neuroscience
Local blood flow is modulated in response to changing patterns of neuronal activity (Roy and Sherrington, 1890), a process termed neurovascular coupling. It has been proposed that the central cellular pathway driving this process is…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Susanna C. Larsson, Paul Carter, Siddhartha Kar et al. · 2020 · PLoS Medicine
BACKGROUND: Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers. METHODS AND FINDINGS: We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corr
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Swarkar Sharma, Xiaochong Gao, Douglas Londoño et al. · 2011 · Human Molecular Genetics
Adolescent idiopathic scoliosis (AIS) is an unexplained and common spinal deformity seen in otherwise healthy children. Its pathophysiology is poorly understood despite intensive investigation. Although genetic underpinnings are clear,…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
R. Grace Walton, Cory M. Dungan, Douglas E. Long et al. · 2019 · Aging Cell
Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although respo
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Elizabeth C. Mormino, Reisa A. Sperling, Avram J. Holmes et al. · 2016 · Neurology
OBJECTIVE: To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies. METHODS: We computed polygenic…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Steven R. H. Beach, Gene H. Brody, Alexandre A. Todorov et al. · 2010 · Psychosomatic Medicine
OBJECTIVE: To examine epigenetic processes linking childhood sex abuse to symptoms of antisocial personality disorder (ASPD) in adulthood and to investigate the possibility that the link between childhood sex abuse and deoxyribonucleic…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Alejandro P. Gutiérrez, José M. Yáñez, Steve Fukui et al. · 2015 · PLoS ONE
Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼ 480 individuals from the Cermaq Canada broodstock pr
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Fumihiko Takeuchi, Masato Isono, Tomohiro Katsuya et al. · 2010 · Circulation
BACKGROUND: Two consortium-based genome-wide association studies have recently identified robust and significant associations of common variants with systolic and diastolic blood pressures in populations of European descent, warranting…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Halvor Knutsen, Esben Moland Olsen, Per Erik Jorde et al. · 2010 · Molecular Ecology
A key question in many genetic studies on marine organisms is how to interpret a low but statistically significant level of genetic differentiation. Do such observations reflect a real phenomenon, or are they caused by confounding factors…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Kirk E. Lohmueller · 2014 · PLoS Genetics
Population genetic studies have found evidence for dramatic population growth in recent human history. It is unclear how this recent population growth, combined with the effects of negative natural selection, has affected patterns of deleterious variation, as well as the number, frequency, and effect sizes of mutations that contribute risk to complex traits. Because researchers are performing exome sequencing studies aimed at uncovering the role of low-frequency variants in the risk of complex traits, this topic is of critical importance. Here I use simulations under population genetic models
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Konstantinos K. Tsilidis, Despoina Capothanassi, Naomi E. Allen et al. · 2014 · Diabetes Care
OBJECTIVE: Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis. RESEARCH DESIGN AND METHODS: A retrospective cohort study,…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Alex Nisthal, Connie Y. Wang, Marylouise Ary et al. · 2019 · Proceedings of the National Academy of Sciences
The accurate prediction of protein stability upon sequence mutation is an important but unsolved challenge in protein engineering. Large mutational datasets are required to train computational predictors, but traditional methods for…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Tim Schneider, Lee-Hsueh Hung, Silke Schreiner et al. · 2016 · Scientific Reports
Circular RNAs (circRNAs) constitute a new class of noncoding RNAs in higher eukaryotes generated from pre-mRNAs by alternative splicing. Here we investigated in mammalian cells the association of circRNAs with proteins. Using glycerol gradient centrifugation, we characterized in cell lysates circRNA-protein complexes (circRNPs) of distinct sizes. By polysome-gradient fractionation we found no evidence for efficient translation of a set of abundant circRNAs in HeLa cells. To identify circRNPs with a specific protein component, we focused on IMP3 (IGF2BP3, insulin-like growth factor 2 binding pr
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Seema A. Khan, Fengmin Zhao, Lori J. Goldstein et al. · 2022 · Journal of Clinical Oncology
PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Elizabeth E. Hong, Cindy Yen Okitsu, Andrew D. Smith et al. · 2013 · Molecular and Cellular Biology
Although CpG methylation clearly distributes genome-wide in vertebrate nuclear DNA, the state of methylation in the vertebrate mitochondrial genome has been unclear. Several recent reports using immunoprecipitation, mass spectrometry, and…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Núria Roura‐Pascual, Cang Hui, Takayoshi Ikeda et al. · 2010 · Proceedings of the National Academy of Sciences
Because invasive species threaten the integrity of natural ecosystems, a major goal in ecology is to develop predictive models to determine which species may become widespread and where they may invade. Indeed, considerable progress has…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Sarah J. Marzi, Karen Sugden, Louise Arseneault et al. · 2018 · American Journal of Psychiatry
OBJECTIVE: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether…
View details →Replication FailureOpen accessBiochemistry, Genetics and Molecular Biology
Ramon Casanova, Sudhir Varma, Brittany Simpson et al. · 2016 · Alzheimer s & Dementia
INTRODUCTION: Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] =…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Carter J. Wilson, Wing‐Yiu Choy, Mikko Karttunen · 2022 · International Journal of Molecular Sciences
The development of AlphaFold2 marked a paradigm-shift in the structural biology community. Herein, we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that AlphaFold2 performs well at discriminating disordered regions, but also note that the disorder predictor one constructs from an AlphaFold2 structure determines accuracy. In particular, a naïve, but non-trivial assumption that residues assigned to helices, strands, and H-bond stabilized turns are likely ordered and all other residues are disordered results in a dra
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Zachary H. Lemmon, Robert Bukowski, Qi Sun et al. · 2014 · PLoS Genetics
Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all s
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Douglas H. Kelley, Nicholas T. Ouellette · 2013 · Scientific Reports
Collective animal behaviour occurs at nearly every biological size scale, from single-celled organisms to the largest animals on earth. It has long been known that models with simple interaction rules can reproduce qualitative features of…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Keun‐Wook Lee, Sung Sook Lee, Sang-Bae Kim et al. · 2014 · Clinical Cancer Research
PURPOSE: Activation of YAP1, a novel oncogene in the Hippo pathway, has been observed in many cancers, including colorectal cancer. We investigated whether activation of YAP1 is significantly associated with prognosis or treatment outcomes…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Noah J Connally, Sumaiya Nazeen, Daniel Lee et al. · 2022 · eLife
-linked genes. However, despite the availability of gene expression and epigenomic datasets, few variant-to-gene links have emerged. It is unclear whether these sparse results are due to limitations in available data and methods, or to deficiencies in the underlying assumed model. To better distinguish between these possibilities, we identified 220 gene-trait pairs in which protein-coding variants influence a complex trait or its Mendelian cognate. Despite the presence of expression quantitative trait loci near most GWAS associations, by applying a gene-based approach we found limited evidence
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Erfan Sayyari, Siavash Mirarab · 2018 · Genes
Phylogenetic species trees typically represent the speciation history as a bifurcating tree. Speciation events that simultaneously create more than two descendants, thereby creating polytomies in the phylogeny, are possible. Moreover, the inability to resolve relationships is often shown as a (soft) polytomy. Both types of polytomies have been traditionally studied in the context of gene tree reconstruction from sequence data. However, polytomies in the species tree cannot be detected or ruled out without considering gene tree discordance. In this paper, we describe a statistical test based on
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