An Introductory Guide to Aligning Networks Using SANA, the Simulated Annealing Network Aligner.

Sequence alignment has had an enormous impact on our understanding of biology, evolution, and disease. The alignment of biological networks holds similar promise. Biological networks generally model interactions between biomolecules such as proteins, genes, metabolites, or mRNAs. There is strong evidence that the network topology-the "structure" of the network-is correlated with the functions performed, so that network topology can be used to help predict or understand function. However, unlike sequence comparison and alignment-which is an essentially solved problem-network comparison and alignment is an NP-complete problem for which heuristic algorithms must be used.Here we introduce SANA, the Simulated Annealing Network Aligner. SANA is one of many algorithms proposed for the arena of biological network alignment. In the context of global network alignment, SANA stands out for its speed, memory efficiency, ease-of-use, and flexibility in the arena of producing alignments between two or more networks. SANA produces better alignments in minutes on a laptop than most other algorithms can produce in hours or days of CPU time on large server-class machines. We walk the user through how to use SANA for several types of biomolecular networks

Summer weather becomes more persistent in a 2 °C world

Heat and rainfall extremes have intensified over the past few decades and this trend is projected to continue with future global warming1–3. A long persistence of extreme events often leads to societal impacts with warm-and-dry conditions severely affecting agriculture and consecutive days of heavy rainfall leading to flooding. Here we report systematic increases in the persistence of boreal summer weather in a multi-model analysis of a world 2 °C above pre-industrial compared to present-day climate. Averaged over the Northern Hemisphere mid-latitude land area, the probability of warm periods lasting longer than two weeks is projected to increase by 4% (2–6% full uncertainty range) after removing seasonal-mean warming. Compound dry–warm persistence increases at a similar magnitude on average but regionally up to 20% (11–42%) in eastern North America. The probability of at least seven consecutive days of strong precipitation increases by 26% (15–37%) for the mid-latitudes. We present evidence that weakening storm track activity contributes to the projected increase in warm and dry persistence. These changes in persistence are largely avoided when warming is limited to 1.5 °C. In conjunction with the projected intensification of heat and rainfall extremes, an increase in persistence can substantially worsen the effects of future weather extremes

A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana)

The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 VH gene segments, 87 DH gene segments (the largest number in mammals examined so far), six JH gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 Vκ gene segments, three Jκ segments, and a single Cκ gene. Two different transcriptional orientations were determined for these Vκ gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 Vλ gene segments, all with the same transcriptional polarity as the downstream Jλ-Cλ cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals

An introductory guide to aligning networks using SANA, the Simulated Annealing Network Aligner

Sequence alignment has had an enormous impact on our understanding of biology, evolution, and disease. The alignment of biological {\em networks} holds similar promise. Biological networks generally model interactions between biomolecules such as proteins, genes, metabolites, or mRNAs. There is strong evidence that the network topology -- the "structure" of the network -- is correlated with the functions performed, so that network topology can be used to help predict or understand function. However, unlike sequence comparison and alignment -- which is an essentially solved problem -- network comparison and alignment is an NP-complete problem for which heuristic algorithms must be used. Here we introduce SANA, the {\it Simulated Annealing Network Aligner}. SANA is one of many algorithms proposed for the arena of biological network alignment. In the context of global network alignment, SANA stands out for its speed, memory efficiency, ease-of-use, and flexibility in the arena of producing alignments between 2 or more networks. SANA produces better alignments in minutes on a laptop than most other algorithms can produce in hours or days of CPU time on large server-class machines. We walk the user through how to use SANA for several types of biomolecular networks. Availability: https://github.com/waynebhayes/SAN

Trabeculectomy and optic nerve head topography

The objective of the present study was to evaluate changes in optic nerve head parameters, measured by confocal laser tomography, before and after trabeculectomy in order to identify outcome measures for the management of glaucoma. The optic nerve head of 22 eyes (22 patients) was analyzed by confocal laser tomography with the Heidelberg retinal tomogram (HRT) before and after trabeculectomy. The median time between the first HRT and surgery was 4.6 months (mean: 7.7 ± 8.3) and the median time between surgery and the second HRT was 10.8 months (mean: 12.0 ± 6.8). The patients were divided into two groups, i.e., those with the highest (group A) and lowest (group B) intraocular pressure (IOP) change after surgery. Differences in the 12 standard topographic parameters before and after surgery for each group were evaluated by the Wilcoxon signed rank test and the differences in these parameters between the two groups were compared by the Mann-Whitney rank sum test. Multiple regression analysis was used to evaluate the influence of the change in IOP (deltaIOP and deltaIOP%) and the changes in the other parameters. There were significant differences in the HRT measures before and after surgery in group A only for cup volume. In group B, no parameter was statistically different. The changes in group A were not significantly different than those in group B for any parameter (P > 0.004, Bonferroni correction for multiple comparisons). deltaIOP and deltaIOP% had a statistically significant effect on delta cup disk area, delta cup volume and delta mean cup depth. Changes in cup shape size were influenced significantly only by deltaIOP. Some optic disc parameters measured by HRT presented a significant improvement after filtering surgery, depending on the amount of IOP reduction. Long-term studies are needed to determine the usefulness of these findings as outcome measures in the management of glaucoma

Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients

Purpose To investigate factors associated with changes in optic nerve head (ONH) topography after acute intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG).Methods Untreated POAG patients (IOP >21 mm Hg) were prospectively enrolled. Systemic and ocular information were collected, including central corneal thickness (CCT) and corneal hysteresis (CH). All patients underwent confocal scanning laser ophthalmoscopy and tonometry (Goldmann) before and 1 h after pharmacological IOP reduction. the mean of three measurements was considered for analysis. Changes in each ONH topographic parameter were assessed (one eye was randomly selected), and those that changed significantly were correlated with patient's systemic and ocular characteristics.Results A total of 42 patients were included (mean age, 66.7 +/- 11.8 years). After a mean IOP reduction of 47.3 +/- 11.9%, significant changes were observed in cup area and volume, and in rim area and volume (P = 0.21, P = 0.12). Including all significant factors in a multivariable model, only the presence of diabetes remained significantly associated with all ONH parameters evaluated (P < 0.01).Conclusions Different systemic and ocular factors, such as diabetes, CH, and the relative size of the cup, seem to be associated with the magnitude of changes in ONH topography after acute IOP reduction in POAG patients. These associations partially explain the ONH changes observed in these patients and suggest that other factors are possibly implicated in an individual susceptibility to IOP. Eye (2011) 25, 201-207; doi:10.1038/eye.2010.179; published online 3 December 2010Universidade Federal de São Paulo, Dept Ophthalmol, BR-820 São Paulo, BrazilNew York Eye & Ear Infirm, Einhorn Clin Res Ctr, New York, NY 10003 USANew York Med Coll, Valhalla, NY 10595 USAUniversidade Federal de São Paulo, Dept Ophthalmol, BR-820 São Paulo, BrazilWeb of Scienc

Short-term changes in the optic nerve head and visual field after trabeculectomy

Aims or Purpose To evaluate short-term changes in optic nerve head topography and visual field induced by surgical reduction of intraocular pressure. Methods A prospective study was performed on 56 eyes of 56 patients with uncontrolled primary open-angle glaucoma despite maximum medical therapy, which underwent trabeculectomy. Optic nerve head evaluations by means of Heidelberg Retina Tomograph, and visual field tests were performed pre-operatively, and at 3 and 6 months after surgery. Differences in intraocular pressure, visual field indices, and Heidelberg Retina Tomograph parameters were evaluated with the t-test for paired data. A linear regression model was calculated to analyze the relationship between intraocular pressure reduction and visual field changes, and optic nerve head changes. Results Mean intraocular pressure decreased from 24.4 +/- 5.0mmHg to 12.1 +/- 3.1mmHg (month 3, P<0.001), and 10.6 +/- 2.8mmHg (month 6, P<0.001) after trabeculectomy. Mean retinal nerve fiber layer thickness (baseline, 0.19 +/- 0.034; month 3, 0.24 +/- 0.039, P=0.05; month 6, 0.21 +/- 0.037, P=0.05) showed a statistical significant change compared with baseline values. Conclusions In this 6-months study, a significant increase in retinal nerve fiber layer thickness was detected after glaucoma filtration surgery. Eye (2011) 25, 1057-1063; doi:10.1038/eye.2011.119; published online 27 May 201