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1.
Surg Endosc ; 37(10): 7901-7907, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37418149

RESUMO

BACKGROUND: Freestanding emergency departments (FSEDs) have generated improved hospital metrics, including decreased ED wait times and increased patient selection. Patient outcomes and process safety have not been evaluated. This study investigates the safety of FSED virtual triage in the emergency general surgery (EGS) patient population. METHODS AND PROCEDURES: A retrospective review evaluated all adult EGS patients admitted to a community hospital between January 2016 and December 2021 who either presented at a FSED and received virtual evaluation from a surgical team (fEGS) or presented at the community hospital emergency department and received in-person evaluation from the same surgical group (cEGS). Patients' demographics, acute care utilization history, and clinical characteristics at the onset of the index visit were used to build a propensity score model and stabilized Inverse Probability of Treatment Weights (IPTW) were used to create a weighted sample. Multivariable regression models were then employed to the weighted sample to evaluate the treatment effect of virtual triage compared to in-person evaluation on short-term outcomes, including length of stay (LOS) and 30-day readmission and mortality. Variables which occurred during the index visit (such as surgery duration and type of surgery) were adjusted for in the multivariable analyses. RESULTS: Of 1962 patients, 631 (32.2%) were initially evaluated virtually (fEGS) and 1331 (67.8%) underwent an in-person evaluation (cEGS). Baseline characteristics demonstrated significant differences between the cohorts in gender, race, payer status, BMI, and CCI score. Baseline risks were well balanced in the IPTW-weighted sample (SD range 0.002-0.18). Multivariable analysis found no significant differences between the balanced cohorts in 30-day readmission, 30-day mortality, and LOS (p > 0.05 for all). CONCLUSION: Patients who undergo virtual triage have similar outcomes to those who undergo in-person triage for EGS diagnoses. Virtual triage at FSED for these EGS patients may be an efficient and safe means for initial evaluation.


Assuntos
Cirurgia Geral , Triagem , Adulto , Humanos , Pontuação de Propensão , Serviço Hospitalar de Emergência , Hospitalização , Tempo de Internação , Estudos Retrospectivos
2.
J Abdom Wall Surg ; 3: 12946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873344

RESUMO

Background: Health disparities are pervasive in surgical care. Particularly racial and socioeconomic inequalities have been demonstrated in emergency general surgery outcomes, but less so in elective abdominal wall reconstruction (AWR). The goal of this study was to evaluate the disparities in referrals to a tertiary hernia center. Methods: A prospectively maintained hernia database was queried for patients who underwent open ventral hernia (OVHR) or minimally invasive surgical (MISR) repair from 2011 to 2022 with complete insurance and address information. Patients were divided by home address into in-state (IS) and out-of-state (OOS) referrals as well as by operative technique. Demographic data and outcomes were compared. Standard and inferential statistical analyses were performed. Results: Of 554 patients, most were IS (59.0%); 334 underwent OVHR, and 220 underwent MISR. IS patients were more likely to undergo MISR (OVHR: 45.6% vs. 81.5%, laparoscopic: 38.2% vs. 14.1%, robotic: 16.2% vs. 4.4%; p < 0.001) when compared to OOS referrals. Of OVHR patients, 44.6% were IS and 55.4% were OOS. Patients' average age and BMI, sex, ASA score, and insurance payer were similar between IS and OOS groups. IS patients were more often Black (White: 77.9% vs. 93.5%, Black: 16.8% vs. 4.3%; p < 0.001). IS patients had more smokers (12.1% vs. 3.2%; p = 0.001), fewer recurrent hernias (45.0% vs. 69.7%; p < 0.001), and smaller defects (155.7 ± 142.2 vs. 256.4 ± 202.9 cm2; p < 0.001). Wound class, mesh type, and rate of fascial closure were similar, but IS patients underwent fewer panniculectomies (13.4% vs. 34.1%; p < 0.001), component separations (26.2% vs. 51.4%; p < 0.001), received smaller mesh (744.2 ± 495.6 vs. 975.7 ± 442.3 cm2; p < 0.001), and had shorter length-of-stay (4.8 ± 2.0 vs. 7.0 ± 5.5 days; p < 0.001). There was no difference in wound breakdown, seroma requiring intervention, hematoma, mesh infection, or recurrence; however, IS patients had decreased wound infections (2.0% vs. 8.6%; p = 0.009), overall wound complications (11.4% vs. 21.1%; p = 0.016), readmissions (2.7% vs. 13.0%; p = 0.001), and reoperations (3.4% vs. 11.4%; p = 0.007). Of MISR patients, 80.9% were IS and 19.1% were OOS. In contrast to OVHR, MISR IS and OOS patients had similar demographics, preoperative characteristics, intraoperative details, and postoperative outcomes. Conclusion: Although there were no differences in referred patients for MISR, this study demonstrates the racial disparities that exist among our IS and OOS complex, open AWR patients. Awareness of these disparities can help clinicians work towards equitable access to care and equal referrals to tertiary hernia centers.

3.
Am Surg ; 90(7): 1916-1918, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38523427

RESUMO

An analysis of ACS-NSQIP open ventral hernia repair (OVHR) data (2017-2019) was performed. Respiratory failure (RF) occurred in 643 patients (1%) and not in 63,213 (99%) (nRF). Respiratory failure patients were older (63.7 vs 57 years, P < .001) and more comorbid: insulin-dependent diabetes (14.7% vs 5.8%, P < .001), COPD (19.4% vs 5.2%, P < .001), BMI (36.0 vs 32.8, P < .001), and current tobacco use (24.9% vs 17.6%, P < .001). Respiratory failure patients had greater ASA scores (ASA 3: 63.3% vs 47.8%, P < .001), bowel resection (8.2% vs 1.3%, P < .001), component separation (20.1% vs 9.0%, P < .001), operative times (178.4 vs 98.8 minutes, P < .001), complications (deep wound infections 3.6% vs 1.0%, organ space infections 13.2% vs 1.0%, wound dehiscence 3.1% vs 0.6%, acute renal failure 11.7% vs 0.1%), and hospital stay (13.7 vs 2.3 days), with fewer home discharges (44.3% vs 96.4%) (all P < .001). Respiratory failure patients had higher mortality compared to nRF (20.2% vs 0.1%, P < .001). Respiratory failure after OVHR is rare but correlates closely with significant wound, systemic, and social complications. Preoperative management of risk factors would be appropriate in high-risk patients.


Assuntos
Hérnia Ventral , Herniorrafia , Complicações Pós-Operatórias , Insuficiência Respiratória , Humanos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/epidemiologia , Hérnia Ventral/cirurgia , Pessoa de Meia-Idade , Herniorrafia/efeitos adversos , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Idoso , Bases de Dados Factuais , Estudos Retrospectivos
4.
Am J Surg ; 238: 115843, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39024729

RESUMO

INTRODUCTION: Active smoking is related to wound and respiratory complications following abdominal wall reconstruction (AWR), but no AWR studies directly compare outcomes of abstinent-smokers (AS), fulfilling four-weeks of smoking cessation, to non-smokers (NS). METHODS: Prospectively maintained institutional database was queried for all AWR between 2012 and 2019. AS and NS were included. Primary outcomes were wound and respiratory complications; secondary outcome was recurrence. Standard statistical analyses were performed. RESULTS: Evaluation included 1088 patients, 305 AS and 783 NS. AS had a lower BMI (31.3 vs 32.7 â€‹kg/m2; P â€‹= â€‹0.004) but increased ASA Class III (51.5% vs 34.5 â€‹%, P â€‹= â€‹0.009), COPD (8.9% vs 4.0 â€‹%, P â€‹= â€‹0.001), comorbidities (6.3 vs 4.7, P < 0.001), and wound class (Class III/IV: 25.3% vs 15.8 â€‹%, P â€‹= â€‹0.003). AS had increased defect size (229 vs 209.1 â€‹cm2; P â€‹= â€‹0.023), use of component separation (CST) (52.5% vs 43.8 â€‹%; P â€‹= â€‹0.010) and hospital stay (6.6 vs 6.2 days, P â€‹= â€‹0.015). Postoperative wound, mesh, and pulmonary infection, respiratory failure, and recurrence were similar. On multivariable regression, wound class and complications predicted recurrence. BMI, panniculectomy and CST predicted wound complications. BMI, CST, and wound class predicted respiratory complications. CONCLUSION: Despite greater patient and hernia complexity, smoking cessation appears to result in similar outcomes to never-smokers in this AWR population.

5.
Am J Surg ; : 115823, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38981838

RESUMO

BACKGROUND: Zenker's diverticulum (ZD) was historically treated with an open transcervical myotomy with diverticulectomy, but endoscopic approaches have gained popularity, though with little recent data. This study aimed to report flexible endoscopic cricopharyngomyotomy (FEC) outcomes, particularly in smaller diverticula. METHODS: Patients with ZD treated with FEC at a tertiary center were reviewed. Patients were grouped by diverticulum size: small (sZD)≤1.5 â€‹cm; medium (mZD) â€‹> â€‹1.5 â€‹cm. RESULTS: Of 30 patients, median age, BMI, sex, and comorbidities were similar between sZD (n â€‹= â€‹18) and mZD (n â€‹= â€‹12). Overall, 80.0 â€‹% had the procedure performed with a needle knife. Median number of clips for mucosotomy closure (5.0[5.0,6.0]vs.7.0[5.0,7.0]clips;p â€‹= â€‹0.051), operative time (59.5[51.0,75.0]vs.74.5[51.0,93.5]minutes;p â€‹= â€‹0.498), length-of-stay (1.0[1.0,1.0]vs.1.0[1.0,1.0]days;p â€‹= â€‹0.397), and follow-up (20.8[1.1,33.4]vs.15.6[5.4,50.4]months;p â€‹= â€‹0.641) were comparable. There were no postoperative leaks; incomplete myotomy occurred in one sZD, yielding a clinical success rate of 96.7 â€‹%. CONCLUSIONS: FEC has a high success rate for ZD and an advantage in small diverticula, difficult to treat with stapling or open technique.

6.
Am J Surg ; 234: 136-142, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38627142

RESUMO

BACKGROUND: Flank and lumbar hernias (FLH) are challenging to repair. This study aimed to establish a reproducible management strategy and analyze elective flank and lumbar repair (FLHR) outcomes from a single institution. METHODS: A prospective analysis using a hernia-specific database was performed examining patients undergoing open FLHR between 2004 and 2021. Variables included patient demographics and operative characteristics. RESULTS: Of 142 patients, 106 presented with flank hernias, and 36 with lumbar hernias. Patients, primarily ASA Class 2 or 3, exhibited a mean age of 57.0 â€‹± â€‹13.4 years and BMI of 30.2 â€‹± â€‹5.7 â€‹kg/m2. Repairs predominantly utilized synthetic mesh in the preperitoneal space (95.1 â€‹%). After 29.9 â€‹± â€‹13.1 months follow-up, wound infections occurred in 8.3 â€‹%; hernia recurrence was 3.5 â€‹%. At 6 months postoperatively, 21.2 â€‹% of patients reported chronic pain with two-thirds of these individuals having preoperative pain. CONCLUSIONS: Open preperitoneal FLHR provides a durable repair with low complication and hernia recurrence rates over 2.5 years of follow-up.


Assuntos
Herniorrafia , Telas Cirúrgicas , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Herniorrafia/métodos , Estudos Prospectivos , Idoso , Recidiva , Hérnia Ventral/cirurgia , Adulto , Resultado do Tratamento , Região Lombossacral/cirurgia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos
7.
Am Surg ; : 31348241241692, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557282

RESUMO

INTRODUCTION: Early after its adoption, minimally invasive surgery had limited usefulness in emergent cases. However, with improvements in equipment, techniques, and skills, laparoscopy in complex and emergency operations expanded substantially. This study aimed to examine the trend of laparoscopy in incarcerated or strangulated ventral hernia repair (VHR) over time. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for laparoscopic repair of incarcerated and strangulated hernias (LIS-VHR) and compared over 2 time periods, 2014-2016 and 2017-2019. RESULTS: The utilization of laparoscopy in all incarcerated or strangulated VHR increased over time (2014-2016: 39.9% (n = 14 075) vs 2017-2019: 46.3% (n = 18 369), P < .001). Though likely not clinically significant, demographics and comorbidities statistically differed between groups (female: 51.7% vs 50.0%, P = .003; age 54.5 ± 13.7 vs 55.4 ± 13.8 years, P < .001; BMI 34.9 ± 8.0 vs 34.6 ± 7.8 kg/m2, P < .001). Patients from 2017 to 2019 were less comorbid (18.9% vs 16.8% smokers, P < .001; 18.2% vs 17.3% diabetic, P = .036; 4.6% vs 4.1% COPD, P = .021) but had higher ASA classification (III: 43.3% vs 45.7%; IV: 2.5% vs 2.7%, P < .001). Hernia types (primary, incisional, recurrent) were similar in each group. Operative time (89.7 ± 59.3 vs 97.4 ± 63.4 min, P < .001) became longer but length-of-stay (1.4 ± 3.3 vs 1.1 ± 2.6 days, P < .001) decreased. There was no statistical difference in surgical complications, medical complications, reoperation, or readmission rates between periods. CONCLUSION: Laparoscopic VHR has become a routine method for treating incarcerated and strangulated hernias, and its utilization continues to increase over time. Clinical outcomes have remained the same while hospital stays have decreased.

8.
BMC Bioinformatics ; 13: 32, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22333114

RESUMO

BACKGROUND: It has been increasingly appreciated that coding sequences harbor regulatory sequence motifs in addition to encoding for protein. These sequence motifs are expected to be overrepresented in nucleotide sequences bound by a common protein or small RNA. However, detecting overrepresented motifs has been difficult because of interference by constraints at the protein level. Sampling-based approaches to solve this problem based on codon-shuffling have been limited to exploring only an infinitesimal fraction of the sequence space and by their use of parametric approximations. RESULTS: We present a novel O(N(log N)2)-time algorithm, CodingMotif, to identify nucleotide-level motifs of unusual copy number in protein-coding regions. Using a new dynamic programming algorithm we are able to exhaustively calculate the distribution of the number of occurrences of a motif over all possible coding sequences that encode the same amino acid sequence, given a background model for codon usage and dinucleotide biases. Our method takes advantage of the sparseness of loci where a given motif can occur, greatly speeding up the required convolution calculations. Knowledge of the distribution allows one to assess the exact non-parametric p-value of whether a given motif is over- or under- represented. We demonstrate that our method identifies known functional motifs more accurately than sampling and parametric-based approaches in a variety of coding datasets of various size, including ChIP-seq data for the transcription factors NRSF and GABP. CONCLUSIONS: CodingMotif provides a theoretically and empirically-demonstrated advance for the detection of motifs overrepresented in coding sequences. We expect CodingMotif to be useful for identifying motifs in functional genomic datasets such as DNA-protein binding, RNA-protein binding, or microRNA-RNA binding within coding regions. A software implementation is available at http://bioinformatics.bc.edu/chuanglab/codingmotif.tar.


Assuntos
Algoritmos , Códon , DNA/química , Motivos de Nucleotídeos , RNA/química , Imunoprecipitação da Cromatina , Genômica , Humanos , Fases de Leitura Aberta , Software , Fatores de Transcrição/metabolismo , Regiões não Traduzidas
9.
BMC Bioinformatics ; 13 Suppl 5: S6, 2012 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-22537010

RESUMO

BACKGROUND: Since RNA molecules regulate genes and control alternative splicing by allostery, it is important to develop algorithms to predict RNA conformational switches. Some tools, such as paRNAss, RNAshapes and RNAbor, can be used to predict potential conformational switches; nevertheless, no existent tool can detect general (i.e., not family specific) entire riboswitches (both aptamer and expression platform) with accuracy. Thus, the development of additional algorithms to detect conformational switches seems important, especially since the difference in free energy between the two metastable secondary structures may be as large as 15-20 kcal/mol. It has recently emerged that RNA secondary structure can be more accurately predicted by computing the maximum expected accuracy (MEA) structure, rather than the minimum free energy (MFE) structure. RESULTS: Given an arbitrary RNA secondary structure S0 for an RNA nucleotide sequence a = a1,..., a(n), we say that another secondary structure S of a is a k-neighbor of S0, if the base pair distance between S0 and S is k. In this paper, we prove that the Boltzmann probability of all k-neighbors of the minimum free energy structure S0 can be approximated with accuracy ε and confidence 1 - p, simultaneously for all 0 ≤ k < K, by a relative frequency count over N sampled structures, provided that N>N(ε,p,K)=Φ⁻¹(p/2K)²/4ε², where Φ(z) is the cumulative distribution function (CDF) for the standard normal distribution. We go on to describe the algorithm RNAborMEA, which for an arbitrary initial structure S0 and for all values 0 ≤ k < K, computes the secondary structure MEA(k), having maximum expected accuracy over all k-neighbors of S0. Computation time is O(n³ · K²), and memory requirements are O(n² · K). We analyze a sample TPP riboswitch, and apply our algorithm to the class of purine riboswitches. CONCLUSIONS: The approximation of RNAbor by sampling, with rigorous bound on accuracy, together with the computation of maximum expected accuracy k-neighbors by RNAborMEA, provide additional tools toward conformational switch detection. Results from RNAborMEA are quite distinct from other tools, such as RNAbor, RNAshapes and paRNAss, hence may provide orthogonal information when looking for suboptimal structures or conformational switches. Source code for RNAborMEA can be downloaded from http://sourceforge.net/projects/rnabormea/ or http://bioinformatics.bc.edu/clotelab/RNAborMEA/.


Assuntos
Algoritmos , Conformação de Ácido Nucleico , RNA/química , Sequência de Bases , Dados de Sequência Molecular , Análise de Sequência de RNA/métodos , Termodinâmica
10.
Nucleic Acids Res ; 38(5): 1711-22, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20044352

RESUMO

Given an RNA sequence and two designated secondary structures A, B, we describe a new algorithm that computes a nearly optimal folding pathway from A to B. The algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an effective search strategy in combinatorial optimization. Folding pathways, sometimes called routes or trajectories, are computed by RNAtabupath in a fraction of the time required by the barriers program of Vienna RNA Package. We benchmark RNAtabupath with other algorithms to compute low energy folding pathways between experimentally known structures of several conformational switches. The RNApathfinder web server, source code for algorithms to compute and analyze pathways and supplementary data are available at http://bioinformatics.bc.edu/clotelab/RNApathfinder.


Assuntos
Algoritmos , RNA/química , Software , Biologia Computacional/métodos , Conformação de Ácido Nucleico , Análise de Sequência de RNA
11.
Innovations (Phila) ; 15(6): 547-554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33090890

RESUMO

OBJECTIVE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy in patients with esophageal carcinoma. Management of DGE varies widely and it is unclear how comorbidities influence the postoperative course. This study sought to determine factors that influence postoperative DGE. METHODS: This retrospective study evaluates patients who underwent esophagectomy with gastric pull-up between 2007 and 2019. The cohort was stratified in various ways to determine if postoperative care and outcomes differed, including patient demographics, comorbidities, intraoperative and postoperative procedures. RESULTS: During the study period, 149 patients underwent esophagectomy and 37 had diabetes. Overall incidence of DGE, as defined in this study, was 76.5%. Surgery type was significantly different between DGE and normal emptying cohorts (P = 0.005). Comparing diabetic and nondiabetic patients, there was no significant difference noted in DGE (P = 0.25). Additionally, there was no difference in presence of DGE for patients who underwent any intraoperative pyloric procedure compared to those who did not (P = 0.36). Of significance, all 16 patients with chronic obstructive pulmonary disease had a delay in gastric emptying (P = 0.01). CONCLUSIONS: A higher proportion of patients with DGE post-esophagectomy were identified compared to the literature. There is little consensus on a true definition of DGE, but we believe this definition identifies patients suffering in the immediate postoperative period and in follow-up. There is no evidence to support a different postoperative course for patients with diabetes, but the link between chronic obstructive pulmonary disease and DGE warrants further investigation.


Assuntos
Esofagectomia , Gastroparesia , Esofagectomia/efeitos adversos , Esvaziamento Gástrico , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Piloro , Estudos Retrospectivos
15.
Physiol Genomics ; 26(1): 46-54, 2006 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-16782841

RESUMO

A previous analysis of serum insulin-like growth factor I (IGF-I) levels in a mouse population (n = 961) derived from a cross of (BALB/cJ x C57BL/6J) F1 females and (C3H/HeJ x DBA/2J) F1 males documented quantitative trait loci (QTL) on chromosomes 1, 10, and 17. We employed a newly developed, random walk-based method to search for three- and four-way allelic combinations that might influence IGF-I levels through nonadditive (conditional or epistatic) interactions among 185 genotyped biallelic loci and with significance defined by experiment-wide permutation (P < 0.05). We documented a three-locus combination in which an epistatic interaction between QTL on paternal-derived chromosomes 5 and 18 had an opposite effect on the phenotype based on the allele inherited at a third locus on maternal-derived chromosome 17. The search also revealed three four-locus combinations that influence IGF-I levels through nonadditive genetic interactions. In two cases, the four-allele combinations were associated with animals having high levels of IGF-I, and, in the third case, a four-allele combination was associated with animals having low IGF-I levels. The multiple-locus genome scan algorithm revealed new IGF-I QTL on chromosomes 2, 4, 5, 7, 8, and 12 that had not been detected in the single-locus genome search and showed that levels of this hormone can be regulated by complex, nonadditive interactions among multiple loci. The analysis method can detect multilocus interactions in a genome scan experiment and may provide new ways to explore the genetic architecture of complex physiological phenotypes.


Assuntos
Fator de Crescimento Insulin-Like I/genética , Locos de Características Quantitativas , Algoritmos , Animais , Passeio de Cromossomo , Cruzamentos Genéticos , Epistasia Genética , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Modelos Genéticos , Fenótipo
16.
J Comput Biol ; 21(3): 201-18, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24559086

RESUMO

We describe four novel algorithms, RNAhairpin, RNAmloopNum, RNAmloopOrder, and RNAmloopHP, which compute the Boltzmann partition function for global structural constraints-respectively for the number of hairpins, the number of multiloops, maximum order (or depth) of multiloops, and the simultaneous number of hairpins and multiloops. Given an RNA sequence of length n and a user-specified integer 0 ≤ K ≤ n, RNAhairpin (resp. RNAmloopNum and RNAmloopOrder) computes the partition functions Z(k) for each 0 ≤ k ≤ K in time O(K(2)n(3)) and space O(Kn(2)), while RNAmloopHP computes the partition functions Z(m, h) for 0 ≤ mm ≤ M multiloops and 0 ≤ h ≤ H hairpins, with run time O(M(2)H(2)n(3)) and space O(MHn(2)). In addition, programs such as RNAhairpin (resp. RNAmloopHP) sample from the low-energy ensemble of structures having h hairpins (resp. m multiloops and h hairpins), for given h, m. Moreover, by using the fast Fourier transform (FFT), RNAhairpin and RNAmloopNum have been improved to run in time O(n(4)) and space O(n(2)), although this improvement is not possible for RNAmloopOrder. We present two applications of the novel algorithms. First, we show that for many Rfam families of RNA, structures sampled from RNAmloopHP are more accurate than the minimum free-energy structure; for instance, sensitivity improves by almost 24% for transfer RNA, while for certain ribozyme families, there is an improvement of around 5%. Second, we show that the probabilities p(k)=Z(k)/Z of forming k hairpins (resp. multiloops) provide discriminating novel features for a support vector machine or relevance vector machine binary classifier for Rfam families of RNA. Our data suggests that multiloop order does not provide any significant discriminatory power over that of hairpin and multiloop number, and since these probabilities can be efficiently computed using the FFT, hairpin and multiloop formation probabilities could be added to other features in existent noncoding RNA gene finders. Our programs, written in C/C++, are publicly available online at: http://bioinformatics.bc.edu/clotelab/RNAparametric .


Assuntos
Biologia Computacional , Sequências Repetidas Invertidas/genética , Conformação de Ácido Nucleico , RNA/química , Algoritmos , Análise de Fourier , Probabilidade , RNA/genética , Análise de Sequência de RNA , Termodinâmica
17.
PLoS One ; 6(1): e16178, 2011 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-21297972

RESUMO

An RNA secondary structure is locally optimal if there is no lower energy structure that can be obtained by the addition or removal of a single base pair, where energy is defined according to the widely accepted Turner nearest neighbor model. Locally optimal structures form kinetic traps, since any evolution away from a locally optimal structure must involve energetically unfavorable folding steps. Here, we present a novel, efficient algorithm to compute the partition function over all locally optimal secondary structures of a given RNA sequence. Our software, RNAlocopt runs in O(n3) time and O(n2) space. Additionally, RNAlocopt samples a user-specified number of structures from the Boltzmann subensemble of all locally optimal structures. We apply RNAlocopt to show that (1) the number of locally optimal structures is far fewer than the total number of structures--indeed, the number of locally optimal structures approximately equal to the square root of the number of all structures, (2) the structural diversity of this subensemble may be either similar to or quite different from the structural diversity of the entire Boltzmann ensemble, a situation that depends on the type of input RNA, (3) the (modified) maximum expected accuracy structure, computed by taking into account base pairing frequencies of locally optimal structures, is a more accurate prediction of the native structure than other current thermodynamics-based methods. The software RNAlocopt constitutes a technical breakthrough in our study of the folding landscape for RNA secondary structures. For the first time, locally optimal structures (kinetic traps in the Turner energy model) can be rapidly generated for long RNA sequences, previously impossible with methods that involved exhaustive enumeration. Use of locally optimal structure leads to state-of-the-art secondary structure prediction, as benchmarked against methods involving the computation of minimum free energy and of maximum expected accuracy. Web server and source code available at http://bioinformatics.bc.edu/clotelab/RNAlocopt/.


Assuntos
Algoritmos , Modelos Moleculares , Conformação de Ácido Nucleico , RNA/química , Sequência de Bases , Internet , Software , Termodinâmica
18.
Pac Symp Biocomput ; : 57-68, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19908358

RESUMO

We describe several dynamic programming segmentation algorithms to segment RNA secondary and tertiary structures into distinct domains. For this purpose, we consider fitness functions that variously depend on (i) base pairing probabilities in the Boltzmann low energy ensemble of structures, (ii) contact maps inferred from 3-dimensional structures, and (iii) Voronoi tessellation computed from 3-dimensional structures. Segmentation algorithms include a direct dynamic programming method, previously discovered by Bellman and by Finkelstein and Roytberg, as well as two novel algorithms - a parametric algorithm to compute the optimal segmentation into k classes, for each value k, and an algorithm that simultaneously computes the optimal segmentation of all subsegments. Since many non-coding RNA gene finders scan the genome by a moving window method, reporting high-scoring windows, we apply structural segmentation to determine the most likely 5' and 3' boundaries of precursor microRNAs. When tested on all precursor microRNAs of length at most 100 nt from the Rfam database, benchmarking studies indicate that segmentation determines the 5' boundary with discrepancy (absolute value of difference between predicted and real boundaries) having mean -0.640 (stdev 15.196) and the 3' boundary with discrepancy having mean -0.266 (stdev. 17.415). This yields a sensitivity of 0.911 and positive predictive value of 0.906 for determination of exact boundaries of precursor microRNAs within a window of approximately 900 nt. Additionally, by comparing the manual segmentation of Jaeger et al. with our optimal structural segmentation of 16S and 16S-like rRNA of E. coli, rat mitochondria, Halobacterium volcanii, and Chlamydomonas reinhardii chloroplast into 4 segments, we establish the usefulness of (automated) structural segmentation in decomposing large RNA structures into distinct domains.


Assuntos
Algoritmos , MicroRNAs/química , Conformação de Ácido Nucleico , Animais , Biologia Computacional , Simulação por Computador , MicroRNAs/genética , Modelos Moleculares , Ratos , Riboswitch/genética
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