Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Improved visualization of peripherally inserted central catheters on chest radiographs of neonates using fractional multiscale image processing

Abstract Background Peripherally inserted central catheters (PICCs) provide secure intravenous access for the delivery of life-sustaining medications and nutrition. They are commonly used in pediatrics. Confirmation of correct central catheter tip position is crucial. Verification is usually done by a radiograph. The aim of this study is to evaluate the ability of Fractional Multiscale image Processing (FMP) to detect PICC tips on the digital chest radiographs of neonates. Methods A total of 94 radiographs of 47 patients were included in the study. 29 patients were male, 18 were female. The mean age of all examined children was 9.2 days (range 0–99 days). In total, six readers (two radiologists, two residents in radiology, one last year medical student, one neonatologist) evaluated 94 unprocessed and catheter-enhanced radiographs using a 5-point Likert scale (1 = poor catheter tip visualization, 5 = excellent catheter tip visualization). Additionally, the two radiologists evaluated the diagnostic confidence for chest pathologies using a 5-point Likert scale (1 = poor diagnostic confidence, 5 = excellent diagnostic confidence). Radiographs were evaluated on a dedicated workstation. Results In all cases, the catheter-enhanced radiograph rated higher than (n = 471), or equal (n = 93) to, the unprocessed radiograph when visualizing catheter tips. 87% of the catheter-enhanced radiographs obtained a rating of 4 or higher, while only 42% of unprocessed radiographs received 4 or more points. Regarding diagnostic confidence for chest pathologies one radiologist rated two catheter-enhanced radiographs higher than the unprocessed radiographs, while all other 186 evaluations rated the catheter-enhanced radiographs equal to (n = 78) or lower than (n = 108) the unprocessed radiographs. Only 60% of the catheter-enhanced radiographs yielded a diagnostic confidence of 4 or higher, while 90% of the unprocessed images received 4 or more points. Conclusion Catheter-enhanced digital chest radiographs demonstrate improved visualization of low contrast PICC tips in neonates compared to unprocessed radiographs. Furthermore, they enable detection of accompanying chest pathologies. However, definitive diagnosis of chest pathologies should be made on unprocessed radiographs

Clinical and molecular characteristics, and their relations to overall survival.

<p>Clinical and molecular characteristics, and their relations to overall survival.</p

Relations of clinical and molecular characteristics to MATH values.

<p>Relations of clinical and molecular characteristics to MATH values.</p

Multivariate relation of MATH value and standard prognostic variables to overall survival.

<p>Multivariate relation of MATH value and standard prognostic variables to overall survival.</p

Relations of clinical and molecular characteristics to MATH values, adjusting for HPV status.

<p>Relations of clinical and molecular characteristics to MATH values, adjusting for HPV status.</p

Clinical and molecular characteristics, and their relations to overall survival.

<p>Clinical and molecular characteristics, and their relations to overall survival.</p

MATH receiver operating characteristic curves.

<p>Time-dependent ROC curves (solid lines) evaluated at 3-y survival, obtained by the nearest neighbor method of Heagerty et al. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001786#pmed.1001786.ref044" target="_blank">44</a>], with a smoothing span of 0.1. Curves show the relation between sensitivity (true-positive fraction) and specificity (1 − false-positive fraction) as the MATH value used to distinguish high- from low-heterogeneity tumors (values shown along the curves) is altered. Dashed lines are lines of identity. Left, ROC curve for all 305 patients (95% CI for AUC, 0.60 to 0.74). Right, ROC curve for 78 patients receiving chemoradiation as primary therapy or as an adjuvant to surgery (95% CI for AUC, 0.54 to 0.82).</p

MATH value and mortality in patients with tumors in the oral cavity or the larynx.

<p>Left, patients with oral-cavity tumors; right, patients with laryngeal tumors. Top, Kaplan-Meier curves for all patients. Blue, low MATH; red, high MATH (MATH > 32). Cox proportional hazards analysis: oral cavity, high/low MATH HR, 1.69 (95% CI, 1.04 to 2.73; <i>p</i> = 0.033); larynx, high/low MATH HR, 3.55 (95% CI, 1.25 to 10.1; <i>p</i> = 0.018). Bottom, joint relation of MATH value and disease stage to survival; dashed, lines Stages I–III; solid lines, Stage IV. Cox proportional hazards analysis: oral cavity, high/low MATH HR, 1.67 (95% CI, 1.03 to 2.70; <i>p</i> = 0.037, Wald test); Stage IV/Stage I–III HR, 1.34 (95% CI, 0.87 to 2.08; <i>p</i> = 0.19); larynx, high/low MATH HR, 3.50 (95% CI, 1.18 to 10.4; <i>p</i> = 0.024); Stage IV/Stage I–III HR, 1.04 (95% CI, 0.44 to 2.49; <i>p</i> = 0.92).</p

Examples of distributions of intra-tumor MAFs and their relation to MATH values.

<p>Density plots (smoothed histograms) of the distributions of MAFs for two HNSCCs. The horizontal-axis position of each circle represents the MAF for a tumor-specific mutated locus in the indicated tumor sample, for loci having MAFs no lower than 0.075: left, 117 loci; right, 106 loci. For each tumor, the median and the MAD of its MAFs are indicated; each tumor MATH value is the percentage ratio of its MAD to its median. The vertical density axis is scaled so that the area under the smoothed curve equals 1; a high peak density value indicates a sharp peak. MAFs of mutated loci in the high-heterogeneity tumor (right panel) show a lower median and higher MAD than those in the low-heterogeneity tumor (left panel), even though the total numbers of mutated loci, a measure of mutation rates within the tumors, are similar.</p