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BMC Bioinformatics Sep 2023The study of de novo variation is important for assessing biological characteristics of new variation and for studies related to human phenotypes. Software programs...
BACKGROUND
The study of de novo variation is important for assessing biological characteristics of new variation and for studies related to human phenotypes. Software programs exist to call de novo variants and programs also exist to test the burden of these variants in genomic regions; however, I am unaware of a program that fits in between these two aspects of de novo variant assessment. This intermediate space is important for assessing the quality of de novo variants and to understand the characteristics of the callsets. For this reason, I developed an R package called acorn.
RESULTS
Acorn is an R package that examines various features of de novo variants including subsetting the data by individual(s), variant type, or genomic region; calculating features including variant change counts, variant lengths, and presence/absence at CpG sites; and characteristics of parental age in relation to de novo variant counts.
CONCLUSIONS
Acorn is an R package that fills a critical gap in assessing de novo variants and will be of benefit to many investigators studying de novo variation.
Topics: Humans; Genomics; Phenotype; Software
PubMed: 37660114
DOI: 10.1186/s12859-023-05457-z -
Incidence and Management of De Novo Lower Urinary Tract Symptoms After Pelvic Organ Prolapse Repair.Current Urology Reports Sep 2017Pelvic organ prolapse (POP) is a significant problem with many options for surgical correction. Following prolapse surgery, de novo lower urinary tract symptoms (LUTS)... (Review)
Review
PURPOSE OF REVIEW
Pelvic organ prolapse (POP) is a significant problem with many options for surgical correction. Following prolapse surgery, de novo lower urinary tract symptoms (LUTS) are not uncommon. We review the current literature on de novo lower urinary tract symptoms following POP repair and discuss the role of urodynamics in the evaluation of the prolapse patient.
RECENT FINDINGS
Patients with occult stress urinary incontinence (SUI) appear to be at higher risk of developing de novo SUI after POP repair. Prolapse reduction in patients undergoing urodynamic evaluation is important. Different types of POP repair influence rates of de novo SUI. Also, prophylactic anti-incontinence procedures at time of POP repair appear to lower the incidence of de novo SUI, but at the cost of increased risk of complications and morbidity. Pre-existing overactive bladder (OAB) symptoms may either improve or persist, and de novo OAB can develop. The specific role of urodynamic study testing for POP is still being determined. Increasingly, women are seeking surgical treatment for POP. Aside from complications related to surgery in general, proper patient counseling is important regarding the risk of development of de novo voiding problems following surgery. Despite a growing body of literature looking at de novo voiding symptoms after prolapse repair, more studies are still needed.
Topics: Aged; Female; Humans; Incidence; Lower Urinary Tract Symptoms; Middle Aged; Pelvic Organ Prolapse; Postoperative Complications; Risk Factors; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urodynamics; Urologic Surgical Procedures
PubMed: 28900856
DOI: 10.1007/s11934-017-0732-5 -
Expert Opinion on Drug Discovery Aug 2010De novo drug design serves as a tool for the discovery of new ligands for macromolecular targets as well as optimization of known ligands. Recently developed tools aim... (Review)
Review
IMPORTANCE OF THE FIELD
De novo drug design serves as a tool for the discovery of new ligands for macromolecular targets as well as optimization of known ligands. Recently developed tools aim to address the multi-objective nature of drug design in an unprecedented manner.
AREAS COVERED IN THIS REVIEW
This article discusses recent advances in de novo drug design programs and accessory programs used to evaluate compounds post-generation.
WHAT THE READER WILL GAIN
The reader is introduced to the challenges inherent in de novo drug design and will become familiar with current trends in de novo design. Furthermore, the reader will be better prepared to assess the value of a tool, and be equipped to design more elegant tools in the future.
TAKE HOME MESSAGE
De novo drug design can assist in the efficient discovery of new compounds with a high affinity for a given target. The inclusion of existing chemoinformatic methods with current structure-based de novo design tools provides a means of enhancing the therapeutic value of these generated compounds.
Topics: Combinatorial Chemistry Techniques; Drug Design; Ligands; Models, Chemical; Software; Structure-Activity Relationship
PubMed: 22827800
DOI: 10.1517/17460441.2010.497534 -
International Urogynecology Journal Jul 2023The objective was to investigate the incidence and risk factors of postoperative de novo stress urinary incontinence (SUI) in stress-continent women following minimally...
INTRODUCTION AND HYPOTHESIS
The objective was to investigate the incidence and risk factors of postoperative de novo stress urinary incontinence (SUI) in stress-continent women following minimally invasive sacrocolpopexy without an anti-incontinence procedure.
METHODS
We completed a multicenter, retrospective cohort study of women undergoing laparoscopic sacrocolpopexy without concurrent anti-incontinence procedures from October 2006 through January 2021.
RESULTS
Of the 169 women who underwent minimally invasive sacrocolpopexy, 17.1% (n=30) developed de novo SUI, and 7.1% eventually underwent a midurethral sling placement. On logistic regression, BMI, preoperative urinary urgency, and history of transvaginal mesh repair were found to be significantly associated with and predictive of de novo SUI. When the concordance index (C-index) was calculated with the model published by Jelovsek et al. for women who developed de novo SUI within 12 months of the prolapse surgery, the current de novo SUI calculator was able to discriminate de novo SUI outcome (C-index = 0.71).
CONCLUSIONS
The incidence of de novo SUI after minimally invasive sacrocolpopexy without anti-incontinence procedure correlates directly with higher BMI, preoperative urinary urgency, and transvaginal mesh history for POP. Preoperative counseling for minimally invasive sacrocolpopexy should include discussing the risk of de novo SUI and preoperative factors that may increase this risk.
Topics: Female; Humans; Pelvic Organ Prolapse; Urinary Incontinence, Stress; Incidence; Retrospective Studies; Suburethral Slings; Postoperative Complications
PubMed: 36645440
DOI: 10.1007/s00192-022-05434-9 -
European Journal of Gastroenterology &... Mar 2021Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver...
BACKGROUND AND AIMS
Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors.
METHODS
This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method.
RESULTS
A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58-86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50).
CONCLUSION
De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients' survival.
Topics: Female; Humans; Liver; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Retrospective Studies; Risk Factors
PubMed: 32317584
DOI: 10.1097/MEG.0000000000001736 -
Neuro-Chirurgie Mar 2023Adamantinomatous craniopharyngioma has a bimodal age distribution occurring in children aged 5-15 years and less frequently in adults aged 45-60 years. The current...
Adamantinomatous craniopharyngioma has a bimodal age distribution occurring in children aged 5-15 years and less frequently in adults aged 45-60 years. The current embryogenetic hypothesis suggests that adamantinomatous craniopharyngioma (ACP) arises from epithelial remnants of the craniopharyngeal duct or Rathke's pouch. It is thought that this tumor exists early on during childhood but remains indolent, growing very slowly until it is diagnosed incidentally or due to symptoms. Recent reports of de novo development of ACP, however, have challenged this theory. Herein, we present a case of an incidentally discovered de novo adamantinomatous craniopharyngioma that was documented to arise de novo on serial MRIs performed for a different indication. To our knowledge, this is the first report of a middle-aged patient who is diagnosed with a de novo ACP documented with contrast-enhanced MRIs of the sella over a 16-year period. This case challenges our current understanding of the pathophysiology of adamantinomatous craniopharyngioma.
Topics: Adult; Middle Aged; Child; Humans; Craniopharyngioma; Pituitary Neoplasms; Magnetic Resonance Imaging
PubMed: 36701980
DOI: 10.1016/j.neuchi.2023.101404 -
Interventional Neuroradiology : Journal... Aug 2022Intracranial dural arteriovenous fistulas (dAVF) account for nearly 10-15% of all arteriovenous malformations. Although the majority of dAVF are effectively cured after...
Intracranial dural arteriovenous fistulas (dAVF) account for nearly 10-15% of all arteriovenous malformations. Although the majority of dAVF are effectively cured after endovascular intervention, there are cases of dAVFs that may recur after radiographic cure. We present the case of a 69-year-old female with de novo formation of three dAVFs in different anatomic locations after successive endovascular treatments. The patient's initial dAVF was identified in the right posterior frontal convexity region and obliterated with transarterial and transvenous embolization. The patient returned eight years later due to left-sided pulsatile tinnitus and a new dAVF in the left greater sphenoid wing region was seen on angiography. This was treated with transvenous embolization with complete resolution. One year later, she developed left sided pulsatile tinnitus again and was found to have a left carotid-cavernous dAVF. This is the first case report to our knowledge of the formation of three de novo dAVFs over multiple years in distinct anatomical locations. We also review the literature regarding de novo dAVFs after endovascular treatment which includes 16 cases. De novo dAVF formation is likely due to numerous factors including changes in venous flow and aberrant vascular development. It is important to further understand the relationship between endovascular treatment and recurrent dAVF formation to prevent subsequent malformations.
PubMed: 35924383
DOI: 10.1177/15910199221118517 -
Trends in Genetics : TIG Apr 2015Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo... (Review)
Review
Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes.
Topics: Animals; Biological Evolution; Evolution, Molecular; Genes; Humans
PubMed: 25773713
DOI: 10.1016/j.tig.2015.02.007 -
Molecular Phylogenetics and Evolution May 2013De novo origination has recently been appreciated to be an important mechanism contributing to the origin of genes. Evidence indicates that de novo originated genes can... (Review)
Review
De novo origination has recently been appreciated to be an important mechanism contributing to the origin of genes. Evidence indicates that de novo originated genes can evolve important and even essential functions rapidly. We present an "adaptation following neutrality" process to explain the evolution of essential function of new genes. How new de novo originated genes become involved in pathways and interact with other old genes, and the exact functions of these new genes, however, remains largely undocumented. Examinations of the function of de novo origin and the function of noncoding RNA genes should become more frequent and appreciated in the future studies.
Topics: Biosynthetic Pathways; Evolution, Molecular; Genes; Genetic Drift; RNA, Untranslated
PubMed: 23454495
DOI: 10.1016/j.ympev.2013.02.013 -
American Journal of Medical Genetics.... Mar 2020Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal...
Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.
Topics: Adolescent; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Child; Child, Preschool; Cytoskeleton; Female; Genetic Testing; Genetic Variation; Humans; Infant; Infant, Newborn; Male; Mosaicism; Mutation; Myocytes, Cardiac; Pediatrics; Pedigree; Sarcomeres
PubMed: 31912959
DOI: 10.1002/ajmg.c.31764