Comparative analysis of algorithms for identifying copy number variation in array CGH data

The aim of the study is comparative analysis of algorithms for identifying copy number variation in array CGH data. Circular Binary segmentation (CBS), CGH segmentation, Price —Smith—Waterman algorithm (the three algorithms are a part of ADaCGH tool) and Cluster Along Chromosome (CLAC) which is not publicly available were studied and used for the analysis of array CGH data. Simulated data set was generated by adding signals of various intensities such as I unit, 11 units and III units representing gains in the copy number (Copy Number Variation, CNV) at random positions corresponding to real probes covering human genome and by adding white Gaussian noise. The white Gaussian noise was generated with the help of program provided by Dr. Nadia Chuzhanova. Two studies of simulated data are carried out in this project (1) The aim of the first study was to investigate the minimum width of CNV (in probes / BAC clones) that can be detected by the all the algorithms for signal intensity of I, II and III units. (2) The aim of the second study was to detect the minimum gap (in probes/BAC clones) between two CNVs of width 2-12 probes /BAC clones by each algorithm for a signal intensity of I, II and 111 units. The results of the study showed that CGH segmentation and CBS can detect a CNV of minimum width 2 BAC clones/probes in simulated data set. However Price-Smith-Waterman algorithm failed to detect any generated CNV. Studies showed that the CNV detection by both algorithms is influenced by noise as well as the width of CNV and the intensity of CNV. The studies also showed that though CBS was able to detect most of the generated CNVs it is more efficient for detection of CNV having higher width. CGH segmentation was more efficient in detection of CNVs that have lower width. Thus CBS and CGH segmentation efficiently can be used for the analysis of array CGH data. The real data set was obtained from 24 malignant peripheral nerve sheath tumour samples and 3 neurofibromas samples (from 27 patients). This data was then analysed with the help of CBS and CGH segmentation on the basis of the results obtained from simulated data set. In general, the ADaCGH is a very good tool for the analysis of array CGH data

Association of baseline hematoma and edema volumes with one-year outcome and long-term survival after spontaneous intracerebral hemorrhage: A community-based inception cohort study

Background Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. Aims In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. Methods We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3–6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. Results Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68–83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9–21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear ( R2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08–2.87); p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63–1.45); p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11–1.42); p = 0.0004). Conclusion Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. Data access statement Anonymized summary data may be requested from the corresponding author. </jats:sec