Part 1. Definition
Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
Part 2. Example
Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Explanation: The question is based on the following sentences from the passage (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) They were also associated with increased blood eosinophilia
Part 3. Exercise
As next-generation sequencing (NGS) becomes a major sequencing platform in clinical diagnostic laboratories, it is critical to identify artifacts that constitute baseline noise and may interfere with detection of low-level gene mutations. This is especially critical for applications requiring ultrasensitive detection, such as molecular relapse of solid tumors and early detection of cancer. We recently observed a ~10-fold higher frequency of C:G>T:A mutations than the background noise level in both wild-type peripheral blood and formalin-fixed paraffin-embedded samples. We hypothesized that these might represent cytosine deamination events, which have been seen using other platforms.', 'To test this hypothesis, we pretreated samples with uracil N-glycosylase (UNG). Additionally, to test whether some of the cytosine deamination might be a laboratory artifact, we simulated the heat associated with polymerase chain reaction thermocycling by subjecting samples to thermocycling in the absence of polymerase. To test the safety of universal UNG pretreatment, we tested known positive samples treated with UNG.', 'UNG pretreatment significantly reduced the frequencies of these mutations, consistent with a biologic source of cytosine deamination. The simulated thermocycling-heated samples demonstrated significantly increased frequencies of C:G>T:A mutations without other baseline base substitutions being affected. Samples with known mutations demonstrated no decrease in our ability to detect these after treatment with UNG.
Answer:
Is cytosine deamination a major cause of baseline noise in next-generation sequencing?