Critical shoulder angle does not influence retear rate after arthroscopic rotator cuff repair.

PURPOSE: The critical shoulder angle (CSA) has been implicated as a potential risk factor for failure following arthroscopic rotator cuff repair (RCR). However, there is conflicting evidence regarding the clinical usefulness of this measurement. Given these discrepancies and limited comparisons to clinical outcomes, the aim of the current study was to determine whether higher CSAs correlated with an increased retear rate after arthroscopic rotator cuff repair and to determine if any association between CSA and patient-reported outcomes (PROs) exists. It was hypothesized that there would be no correlation between CSA and retear rate or PROs after arthroscopic rotator cuff repair. METHODS: A total of 164 patients who underwent arthroscopic RCR were retrospectively reviewed. CSA was measured for each patient. Patients were then divided into a retear group of 18 patients and a non-retear group of 146 patients. Patient-reported outcomes (PROs), including PROMIS 10 score, American Shoulder and Elbow Surgeons (ASES) score, Brophy score, and visual analog pain scores (VAS) were recorded post-operatively. RESULTS: The average CSA was 31.2 ± 4.5° for the retear group and 32.2 ± 4.7° for the non-retear group (n.s.). No correlations were found between CSA and PROMIS score (n.s.), ASES score (n.s.), Brophy score (n.s.), or VAS (n.s.). CONCLUSION: Critical shoulder angle had no correlation to retear rate or patient-reported outcomes. CSA should not be used as a clinical predictor to assess rotator cuff retear risk after arthroscopic RCR. LEVEL OF EVIDENCE: Level III.

Effective management of severe cutaneous mastocytosis in young children with omalizumab (Xolair® ).

Omalizumab (Xolair® ) is an anti-IgE monoclonal antibody, which may benefit adults with systemic mastocytosis. We report effective treatment with omalizumab in two toddlers with severe diffuse cutaneous mastocytosis. Our cases offer preliminary evidence to support the safe use of omalizumab in paediatric patients with cutaneous mastocytosis.

Activated STING in a vascular and pulmonary syndrome.

BACKGROUND: The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS: We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-ß, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS: We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. CONCLUSIONS: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).

A multifaceted pharmacist intervention to improve antihypertensive adherence: a cluster-randomized, controlled trial (HAPPy trial).

WHAT IS KNOWN AND OBJECTIVES: About half of all patients taking antihypertensives discontinue treatment by 12 months. There is potential for substantial health gains at both individual and population levels through improved treatment adherence. The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control. DESIGN: prospective, non-blinded, cluster-randomized, controlled trial. PARTICIPANTS: adults with primary hypertension who obtained antihypertensives in the previous 6 months. Patients with poor refill adherence were preferentially identified with the help of a purpose-built software application. INTERVENTION: package comprising BP monitor; training on BP self-monitoring; motivational interviewing; medication use review; prescription refill reminders. FOLLOW-UP: six months. PRIMARY OUTCOME: change in proportion self-reporting medication adherence. Secondary outcome: BP changes. RESULTS: Participants (n = 395; intervention - 207; control - 188) had a mean age of 66.7 years; 51.1% were males. The proportion of adherent participants increased in both groups but was not significantly different between groups [57·2% to 63·6% (control) vs. 60·0% to 73·5% (intervention), P = 0·23]. The mean reduction in systolic BP was significantly greater in the intervention group (10·0 mmHg vs. 4·6 mmHg; P = 0·05). The proportion of patients who were non-adherent at baseline and adherent at 6 months was 22·6% (95%CI 5·1-40·0%) higher in the intervention group (61·8% vs. 39·2%, P = 0·007). Among participants with baseline BP above target, reduction of systolic BP was significantly greater in the intervention group [by 7·2 mmHg (95%CI 1·6-12·8 mmHg); (P = 0·01)]. Among participants non-adherent at baseline and above target BP, the proportion reporting adherence at 6 months was significantly greater in the intervention group [56·8% vs. 35·9%, P = 0·039). WHAT IS NEW AND CONCLUSION: This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.

Bacterial chondronecrosis with osteomyelitis in broilers: influence of sires and straight-run versus sex-separate rearing.

Two experiments (E1, E2) were conducted to compare the influence of sires (sire A on dam C vs. sire B on dam C) and straight-run versus sex-separate rearing on the incidence of bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Fertile eggs from commercial breeder flocks were incubated and hatched at the University of Arkansas Poultry Research Hatchery. Male and female chicks were reared together (straight-run) or separately (sex-separate) in 3 × 3 m pens on litter or flat wire flooring with 65 (E1) or 60 (E2) birds per pen. Necropsies revealed lesions that are pathognomonic for BCO in ≥98% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative BCO incidences through 8 wk of age. For birds reared on litter, the incidences of BCO were low regardless of cross or sex (range: 1.7 to 5.1%; P ≥ 0.6). Within a cross and sex, rearing the broilers straight-run versus sex-separate on wire flooring did not significantly affect the incidence of BCO. Significant incidences of BCO did not develop until after d 40. Males from the sire A cross developed a higher incidence of BCO than males from the sire B cross in E1 (27 vs. 17%, respectively; P = 0.009) but not in E2 (28.5 vs. 22.6%, respectively; P = 0.141). In both experiments, males from the sire A cross developed higher incidences of BCO than females from the sire B cross (27 vs. 11.9%, in E1; 28.5 vs. 14.8%, in E2). With the sexes pooled, broilers from the sire A cross consistently developed higher incidences of BCO than broilers from the sire B cross (21.4 vs. 14.9%, P = 0.005 in E1; 26.5 vs. 18.7%, P = 0.003 in E2). High susceptibilities to both femoral head (all femoral head necrosis = 66 to 85% incidences) and tibial head (all tibial head necrosis = 81 to 96% incidences) BCO lesions were demonstrated in lame birds from both sexes and crosses. This study supports a sire influence on the susceptibility of broilers to BCO. Sire lines can be chosen to reduce BCO susceptibility when broilers are grown beyond 6 wk of age.

A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression.

Chromosome correlation maps display correlations between the expression patterns of genes on the same chromosome. Using these maps, we show here that adjacent pairs of genes, as well as nearby non-adjacent pairs of genes, show correlated expression independent of their orientation. We present specific examples of adjacent pairs with highly correlated expression patterns, in which the promoter of only one of the two genes contains an upstream activating sequence (UAS) known to be associated with that expression pattern. Finally, we show that genes with similar functions tend to occur in adjacent positions along the chromosomes. Our results suggest that, in certain chromosomal expression domains, an UAS can affect the transcription of genes that are not immediately downstream from it.

Systematic determination of genetic network architecture.

Technologies to measure whole-genome mRNA abundances and methods to organize and display such data are emerging as valuable tools for systems-level exploration of transcriptional regulatory networks. For instance, it has been shown that mRNA data from 118 genes, measured at several time points in the developing hindbrain of mice, can be hierarchically clustered into various patterns (or 'waves') whose members tend to participate in common processes. We have previously shown that hierarchical clustering can group together genes whose cis-regulatory elements are bound by the same proteins in vivo. Hierarchical clustering has also been used to organize genes into hierarchical dendograms on the basis of their expression across multiple growth conditions. The application of Fourier analysis to synchronized yeast mRNA expression data has identified cell-cycle periodic genes, many of which have expected cis-regulatory elements. Here we apply a systematic set of statistical algorithms, based on whole-genome mRNA data, partitional clustering and motif discovery, to identify transcriptional regulatory sub-networks in yeast-without any a priori knowledge of their structure or any assumptions about their dynamics. This approach uncovered new regulons (sets of co-regulated genes) and their putative cis-regulatory elements. We used statistical characterization of known regulons and motifs to derive criteria by which we infer the biological significance of newly discovered regulons and motifs. Our approach holds promise for the rapid elucidation of genetic network architecture in sequenced organisms in which little biology is known.

Public perceptions of the role of Australian pharmacists in cardiovascular disease.

BACKGROUND AND OBJECTIVE: To assess the public's perception of pharmacists' involvement and role in cardiovascular disease prevention and management. METHODS: A computer-assisted telephone interview of 505 households was conducted. The survey was administered to metropolitan, rural and remote residents over the age of 30 years. The interview had questions on the patient's general satisfaction with the quality of service provided by their regular community pharmacy, including factors such as location, professionalism, prices, product range and knowledge of the staff. The participants were asked if they thought pharmacists were capable of providing screening, testing and drug prescribing services for blood pressure and cholesterol, and how likely they would be to use these services through a pharmacy. The interview also included questions on how likely this person would be to seek advice on lifestyle changes and medications from various health professionals, including pharmacists. RESULTS: The majority (97%) were satisfied with the service provided at their regular pharmacy. Those surveyed agreed or strongly agreed that pharmacists are capable of providing screening or testing for raised blood pressure (52%) and diabetes (51%), with a minority (38%) agreeing that pharmacists are capable of testing for raised cholesterol. The pharmacist's role with perceived highest capability by those surveyed was in providing advice on how to take medicines properly, with 90% of respondents willing to seek this advice from their pharmacist. A limited role by pharmacists was seen in the diagnosis of CVD and prescribing medications. In relation to the prevention of CVD, even though 76% of respondents believed that pharmacists are capable of providing advice on lifestyle changes (e.g. weight loss, smoking and alcohol intake), only 8% of current or past smokers had sought assistance to give up smoking at their pharmacy and while 69% of all respondents had sought help with weight control, only 3% of these had looked towards their pharmacy for assistance. CONCLUSION: There was belief by those Australians surveyed that community pharmacists are capable of providing screening for hypertension and diabetes. Through these services and in conjunction with counselling on CVD risk reduction, pharmacists may play an important role in the reduction of CVD, ultimately improving public health and decreasing the burden on Australia's health care system. However, at present pharmacists are not being fully utilized to deliver health promotion advice and contribute to the prevention of CVD.

Sequence diversity among badnavirus isolates infecting yam (Dioscorea spp.) in Ghana, Togo, Benin and Nigeria.

We analysed the sequence diversity in the reverse transcriptase (RT)/ribonuclease H (RNaseH) coding region of 19 badnavirus isolates infecting yam (Dioscorea spp.) in Ghana, Togo, Benin, and Nigeria. Phylogenetic analysis of the deduced amino acid sequences revealed that the isolates are broadly divided into two distinct species, each clustering with Dioscorea alata bacilliform virus (DaBV) and Dioscorea sansibarensis bacilliform virus (DsBV). Fourteen isolates had 90-96% amino acid identity with DaBV, while four isolates had 83-84% amino acid identity with DsBV. One isolate from Benin, BN4Dr, was distinct and had 77 and 75% amino acid identity with DaBV and DsBV, respectively, and may be a member of a new badnavirus species infecting yam in West Africa. Viruses of the two main species were present in Ghana, Togo and Benin and were observed to infect both D. alata and D. rotundata indiscriminately. This is the first confirmed report of DsBV infection in yam in Ghana and Togo. The results of this study demonstrate that members of two distinct species of badnaviruses infect yam in the West African yam zone and suggest a putative new species, BN4Dr. We also conclude that these species are not confined to limited geographic regions or specific for yam host species. However, the three badnavirus species are serologically related. The sequence information obtained from this study can be used to develop PCR-based diagnostics to detect members of the various species and/or strains of badnaviruses infecting yam in West Africa.

Allergic Contact Dermatitis and Autoeczematization to Proctosedyl® Cream and Proctomyxin® Cream.

Proctosedyl® and Proctomyxin® are two commonly prescribed hemorrhoid therapies. Their topical application to the perianal region may be complicated by a local allergic contact dermatitis and subsequent autoeczematization reaction. We present three cases of an autoeczematization (ID) reaction to varying topical allergens found in Proctosedyl®/Proctomyxin®. It is our recommendation that physician and patient education, avoidance of allergens (or cross-reactants), and appropriate choice of topical corticosteroid is important in preventing and avoiding flares.

Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation.

Whole-genome mRNA quantitation can be used to identify the genes that are most responsive to environmental or genotypic change. By searching for mutually similar DNA elements among the upstream non-coding DNA sequences of these genes, we can identify candidate regulatory motifs and corresponding candidate sets of coregulated genes. We have tested this strategy by applying it to three extensively studied regulatory systems in the yeast Saccharomyces cerevisiae: galactose response, heat shock, and mating type. Galactose-response data yielded the known binding site of Gal4, and six of nine genes known to be induced by galactose. Heat shock data yielded the cell-cycle activation motif, which is known to mediate cell-cycle dependent activation, and a set of genes coding for all four nucleosomal proteins. Mating type alpha and a data yielded all of the four relevant DNA motifs and most of the known a- and alpha-specific genes.

Divergent selection for ascites incidence in chickens.

Chicken lines that were either resistant or susceptible to ascites syndrome were developed by using a hypobaric chamber to induce the disease. Birds were reared in a hypobaric chamber that simulated high altitude by operating under a partial vacuum, which thereby lowered the partial pressure of oxygen. Ascites mortality data from birds reared under hypobaric chamber conditions were used to select siblings to be used for breeding. The response to selection for the susceptible (SUS) and resistant (RES) lines of chickens was very rapid from the base population, which exhibited an incidence of ascites of 75.3%. Extremes in the incidence of ascites were observed in generation 8, with line SUS exhibited an average incidence of ascites of 95.1%, and in generation 9, with line RES exhibited an average incidence of ascites of 7.1%. The incidence of ascites in the relaxed line remained relatively stable and currently has a general incidence of ascites of 60%. The heritability estimates +/- SE for ascites were estimated to be 0.30 +/- 0.05 and 0.55 +/- 0.05 for lines SUS and RES, respectively. Changes in the incidence of ascites appeared to be associated with livability. By generation 10, selection for ascites in line RES increased livability by 11.5 d, whereas in line SUS, livability was decreased by 8 d. Although divergent selection for ascites resulted in a reduction in d 42 BW for both the SUS and RES lines, the SUS line was approximately 163 g heavier than the RES line. Negative genetic correlations between ascites and the right ventricle:total ventricle (RV:TV) ratio were observed in both the SUS and RES lines; however, no significant change in the RV:TV ratio was observed for birds reared under normal conditions in either line. The current data raise questions about the validity of using the RV:TV ratio as an indicator trait in a selection program designed to reduce the incidence of ascites. Overall, direct selection for resistance to ascites by using sire family performance appeared to be an effective means of reducing the incidence of ascites. However, simultaneous selection for BW should be applied to counterbalance the losses in correlated BW.

A survey of senior medical students' attitudes and awareness toward teaching and participation in a formal clinical teaching elective: a Canadian perspective.

BACKGROUND: To prepare for careers in medicine, medical trainees must develop clinical teaching skills. It is unclear if Canadian medical students need or want to develop such skills. We sought to assess Canadian students' perceptions of clinical teaching, and their desire to pursue clinical teaching skills development via a clinical teaching elective (CTE) in their final year of medical school. METHODS: We designed a descriptive cross-sectional study of Canadian senior medical students, using an online survey to gauge teaching experience, career goals, perceived areas of confidence, and interest in a CTE. RESULTS: Students at 13 of 17 Canadian medical schools were invited to participate in the survey (4154 students). We collected 321 responses (7.8%). Most (75%) respondents expressed confidence in giving presentations, but fewer were confident providing bedside teaching (47%), teaching sensitive issues (42%), and presenting at journal clubs (42%). A total of 240 respondents (75%) expressed interest in participating in a CTE. The majority (61%) favored a two week elective, and preferred topics included bedside teaching (85%), teaching physical examination skills (71%), moderation of small group learning (63%), and mentorship in medicine (60%). CONCLUSION: Our study demonstrates that a large number of Canadian medical students are interested in teaching in a clinical setting, but lack confidence in skills specific to clinical teaching. Our respondents signaled interest in participating in an elective in clinical teaching, particularly if it is offered in a two-week format.

ERBIN deficiency links STAT3 and TGF-ß pathway defects with atopy in humans.

Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-ß activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-ß signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative STAT3 mutations (STAT3mut ) or a loss-of-function mutation in ERBB2IP (ERBB2IPmut ) have evidence of deregulated TGF-ß signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-ß. In turn, cell-intrinsic deregulation of TGF-ß signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-ß pathway activation in ERBB2IPmut and STAT3mut patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.

Studies on Maize streak virus and Maize mottle/chlorotic stunt virus in Lagos, Nigeria.

Despite the development and deployment of maize streak-resistant (SR) germ plasm, virus-induced symptoms are still commonly observed on maize in Lagos, Nigeria. Therefore, surveys were conducted between April 2001 and February 2002 to determine the identity, prevalence, and incidence of maize viruses in 18 local government areas (LGAs) in and around Lagos by visual examination and serodiagnostic screening of symptomatic plants. All 112 fields surveyed during the dry season (September to December) and 18 fields surveyed during the late dry season (December to February) had plants infected by Maize streak virus (MSV), whereas 97.1% of the 170 fields surveyed during the wet season (April to August) had plants infected by MSV. Maize mottle/chlorotic stunt virus (MMCSV) was prevalent in 99.1, 88.9, and 67.4% of the fields surveyed during the dry, late dry, and wet seasons, respectively. The incidence of MSV was higher in 16 of the LGAs. The highest incidence of MSV was 18.9%, whereas that of MMCSV was 7.4%. Serodiagnostic screening of leaf samples showing virus-induced symptoms, using antigen-coated plate enzyme-linked immunosorbent assay, indicated that 1,192/1,475 (80.8%) and 949/1,210 (78.4%) of the samples were positive for MSV and MMCSV, respectively. Vector transmission and host range studies confirmed the identity of the viruses. The results confirm the presence of MSV and MMCSV in Lagos and suggest that the use of MSV-susceptible cultivars is still widespread. Methods of ensuring effective utilization of existing SR germ plasm and controlling maize viruses in general are discussed.

Status of Cassava Begomoviruses and Their New Natural Hosts in Nigeria.

A diagnostic survey was conducted in 2002-03 to determine the status of cassava mosaic begomoviruses in Nigeria and to ascertain if the virulent Ugandan variant of East African cassava mosaic virus (EACMV-Ug2) was present. Of the 418 farms visited, 48% had cassava with moderately severe or severe symptoms, whereas 52% had cassava with mild symptoms. These distributions were at random. Of the 1,397 cassava leaf samples examined, 1,106 had symptoms. In polymerase chain reaction tests, 74.1% of the symptom-bearing samples tested positive for African cassava mosaic virus (ACMV) alone, 0.3% for EACMV alone, 24.4% for mixed infections by the two viruses, and 1.2% did not react with any of the primers used. The two viruses also were detected in 32% of the 291 symptomless plants and in the whitefly vector samples. EACMV-Ug2, Indian cassava mosaic virus, and South African cassava mosaic virus were not detected in any of the whitefly or leaf samples. Most farms had ACMV in single infection as well as in mixed infections with EACMV. Most doubly infected plants showed severe symptoms. Two biological variants of ACMV were identified based on symptom expression on cassava in the field. ACMV and EACMV were detected in the leguminous plant Senna occidentalis (L.) Link and the weed Combretum confertum Lams.; these are new natural hosts of the viruses. Although the virulent EACMV-Ug2 was not detected, the occurrence of variants of ACMV and a high proportion of mixed infections by ACMV and EACMV, which could result in recombination events such as the one that produced EACMV-Ug2, demands appropriate measures to safeguard cassava production in Nigeria.

Student perceptions of independent versus facilitated small group learning approaches to compressed medical anatomy education.

The purpose of this study was to compare student perceptions regarding two, small group learning approaches to compressed (46.5 prosection-based laboratory hours), integrated anatomy education at the University of Ottawa medical program. In the facilitated active learning (FAL) approach, tutors engage students and are expected to enable and balance both active learning and progression through laboratory objectives. In contrast, the emphasized independent learning (EIL) approach stresses elements from the "flipped classroom" educational model: prelaboratory preparation, independent laboratory learning, and limited tutor involvement. Quantitative (Likert-style questions) and qualitative data (independent thematic analysis of open-ended commentary) from a survey of students who had completed the preclerkship curriculum identified strengths from the EIL (promoting student collaboration and communication) and FAL (successful progression through objectives) approaches. However, EIL led to student frustration related to a lack of direction and impaired completion of objectives, whereas active learning opportunities in FAL were highly variable and dependent on tutor teaching style. A "hidden curriculum" was also identified, where students (particularly EIL and clerkship students) commonly compared their compressed anatomy education or their anatomy learning environment with other approaches. Finally, while both groups highly regarded the efficiency of prosection-based learning and expressed value for cadaveric-based learning, student commentary noted that the lack of grade value dedicated to anatomy assessment limited student accountability. This study revealed critical insights into small group learning in compressed anatomy education, including the need to balance student active learning opportunities with appropriate direction and feedback (including assessment).

Scripting MODFLOW Model Development Using Python and FloPy.

Graphical user interfaces (GUIs) are commonly used to construct and postprocess numerical groundwater flow and transport models. Scripting model development with the programming language Python is presented here as an alternative approach. One advantage of Python is that there are many packages available to facilitate the model development process, including packages for plotting, array manipulation, optimization, and data analysis. For MODFLOW-based models, the FloPy package was developed by the authors to construct model input files, run the model, and read and plot simulation results. Use of Python with the available scientific packages and FloPy facilitates data exploration, alternative model evaluations, and model analyses that can be difficult to perform with GUIs. Furthermore, Python scripts are a complete, transparent, and repeatable record of the modeling process. The approach is introduced with a simple FloPy example to create and postprocess a MODFLOW model. A more complicated capture-fraction analysis with a real-world model is presented to demonstrate the types of analyses that can be performed using Python and FloPy.

Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae.

AlignACE is a Gibbs sampling algorithm for identifying motifs that are over-represented in a set of DNA sequences. When used to search upstream of apparently coregulated genes, AlignACE finds motifs that often correspond to the DNA binding preferences of transcription factors. We previously used AlignACE to analyze whole genome mRNA expression data. Here, we present a more detailed study of its effectiveness as applied to a variety of groups of genes in the Saccharomyces cerevisiae genome. Published functional catalogs of genes and sets of genes grouped by common name provided 248 groups, resulting in 3311 motifs. In conjunction with this analysis, we present measures for gauging the tendency of a motif to target a given set of genes relative to all other genes in the genome and for gauging the degree to which a motif is preferentially located in a certain distance range upstream of translational start sites. We demonstrate improved methods for comparing and clustering sequence motifs. Many previously identified cis-regulatory elements were found. We also describe previously unidentified motifs, one of which has been verified by experiments in our laboratory. An extensive set of AlignACE runs on randomly selected sets of genes and on sets of genes whose upstream regions contain known transcription factor binding sites serve as controls.