Mining gene expression data by interpreting principal components

BACKGROUND: There are many methods for analyzing microarray data that group together genes having similar patterns of expression over all conditions tested. However, in many instances the biologically important goal is to identify relatively small sets of genes that share coherent expression across only some conditions, rather than all or most conditions as required in traditional clustering; e.g. genes that are highly up-regulated and/or down-regulated similarly across only a subset of conditions. Equally important is the need to learn which conditions are the decisive ones in forming such gene sets of interest, and how they relate to diverse conditional covariates, such as disease diagnosis or prognosis. RESULTS: We present a method for automatically identifying such candidate sets of biologically relevant genes using a combination of principal components analysis and information theoretic metrics. To enable easy use of our methods, we have developed a data analysis package that facilitates visualization and subsequent data mining of the independent sources of significant variation present in gene microarray expression datasets (or in any other similarly structured high-dimensional dataset). We applied these tools to two public datasets, and highlight sets of genes most affected by specific subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically significant associations for highlighted gene sets were shown via global analysis for Gene Ontology term enrichment. Together with covariate associations, the tool provides a basis for building testable hypotheses about the biological or experimental causes of observed variation. CONCLUSION: We provide an unsupervised data mining technique for diverse microarray expression datasets that is distinct from major methods now in routine use. In test uses, this method, based on publicly available gene annotations, appears to identify numerous sets of biologically relevant genes. It has proven especially valuable in instances where there are many diverse conditions (10's to hundreds of different tissues or cell types), a situation in which many clustering and ordering algorithms become problematic. This approach also shows promise in other topic domains such as multi-spectral imaging datasets

Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens

An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery

Background An investigation was undertaken to compare the effect of multi-component compression bandages and compression hosiery kits on individuals’ range of ankle motion whilst wearing typical and medical footwear, and barefoot. Methods A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. Results Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54° at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12° at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51° at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. Conclusions Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types

The effectiveness of a low-intensity problem-solving intervention for common adolescent mental health problems in New Delhi, India: protocol for a school-based, individually randomized controlled trial with an embedded stepped-wedge cluster randomized controlled recruitment trial

Background Conduct, anxiety and depressive disorders account for over 75% of the adolescent mental health burden globally. The current protocol will test a low-intensity problem-solving intervention for school-going adolescents with common mental health problems in India. The protocol also tests the effects of a classroom-based sensitization intervention on the demand for counselling services in an embedded recruitment trial. Methods We will conduct a two-arm individually randomized controlled trial in six Government-run secondary schools in New Delhi. The targeted sample is 240 adolescents in grades 9-12 with persistent, elevated mental health symptoms and associated impact. Participants will receive either a brief problem-solving intervention delivered over 3 weeks by lay counsellors (intervention), or enhanced usual care comprised of problem-solving booklets (control). Self-reported adolescent mental health symptoms and idiographic problems will be assessed at 6 weeks (co-primary outcomes) and again at 12 weeks post-randomization. In addition, adolescent-reported impact of mental health difficulties, perceived stress, mental wellbeing and clinical remission, as well as parent-reported adolescent mental health symptoms and impact scores, will be assessed at 6 and 12 weeks post-randomization. We will also complete a parallel process evaluation, including estimations of the costs of delivering the interventions. An embedded recruitment trial will apply a stepped-wedge, cluster (class)-randomized controlled design in 70 classes across the six schools. This will evaluate the added impact of a classroom-based sensitization intervention over school-level recruitment sensitization activities on the primary outcome of referral rate into the host trial (i.e. the proportion of adolescents referred as a function of the total sampling frame in each condition of the embedded recruitment trial). Other outcomes will be the proportion of referrals eligible to participate in the host trial, proportion of self-generated referrals, and severity and pattern of symptoms among referred adolescents in each condition. Power calculations were undertaken separately for each trial. A detailed statistical analysis plan will be developed separately for each trial prior to unblinding. Discussion Both trials were initiated on 20 August 2018. A single research protocol for both trials offers a resource-efficient methodology for testing the effectiveness of linked procedures to enhance uptake and outcomes of a school-based psychological intervention for common adolescent mental health problems

Characterizing Ham and Loin Quality as Hot Carcass Weight Increases to an Average of 119 Kilograms

The objective was to characterize ham and loin quality of carcasses ranging from 78 to 145 kg (average ∼119 kg). Hot carcass weight (HCW), back fat depth, and loin depth was measured on 666 carcasses. Loin pH, instrumental and visual color and iodine value of clear plate fat (all 3 layers) was measured on approximately 90% of the population. Quality measurements of the ham, 14 d aged loin and chop, and loin chop shear force (SSF) were evaluated on approximately 30% of the population. Myosin heavy chain fiber type determination was completed on 49 carcasses. Slopes of regression lines and coefficients of determination between HCW and quality traits were calculated using the REG procedure in SAS and considered significantly different from 0 at P ≤ 0.05. As HCW increased, loin depth (b1 = 0.2496, P 0.15) and did not explain more than 1% (R2 ≤ 0.01) of the variation in 1 d loin color or pH. Loins from heavier carcasses were more tender (decreased SSF; b1 = –0.0674, P 0.22) muscle fiber type percentage or area. These results suggest that increasing HCW to an average of 119 kg did not compromise pork quality

Effects of Increased Pork Hot Carcass Weights. II: Loin Quality Characteristics and Palatability Ratings

The objective of this study was to evaluate the effects of increased pork hot carcass weight on loin quality and palatability of top loin chops. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: A light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119.1 kg), medium-heavy weight (MHVY; 119.1 to 124.4), and a heavyweight group (HVY; 124.4 and greater). Following fabrication, chops were assigned to fat and moisture analysis, Warner-Bratzler shear force (WBSF), consumer sensory panels, or trained sensory panels. Chops from the HVY group were rated as more (P 0.05) consumer flavor liking ratings. Hot carcass weight treatment did not contribute (P > 0.05) to the percentage of chops rated acceptable for flavor and overall liking. The greatest (P 0.05), with greater (P < 0.05) overall tenderness ratings compared to chops from LT carcasses. These results indicate chops from heavier weight carcasses may have improved tenderness and juiciness compared to chops from lighter carcasses

Effects of Increased Pork Hot Carcass Weights. I: Chop Thickness Impact on Consumer Visual Ratings

The objective of this study was to evaluate the effect of increased pork hot carcass weights on consumer visual acceptability and purchase intent ratings of top loin chops cut to various thicknesses in a price labeled versus unlabeled retail display scenario. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119. kg), medium-heavy weight (MHVY; 119.1 to 124.4 kg), and a heavy weight group (HVY; 124.4 kg and greater). Loins were fabricated into 4 pairs of chops of specified thicknesses (1.27, 1.91, 2.54, and 3.18 cm). One chop from each pair was assigned to be packaged with or without a label. Consumers assessed chops for appearance, desirability, and purchase intent. For both appearance and purchase intent ratings, chops from HVY carcasses were given more desirable (P < 0.05) ratings compared to LT chops. Consumers gave greater (P < 0.05) appearance ratings to thicker cut chops. There was a hot carcass weight × chop thickness interaction (P < 0.05) for the percentage of consumers that indicated the chop was desirable overall. Regardless of hot carcass weight group, chops with a thickness of 1.27 cm had the lowest (P < 0.05) percentage of consumers indicate they were desirable overall. A greater (P < 0.05) percentage of consumers indicated “yes” they would purchase chops cut to a thickness of 2.54 cm compared to all other thicknesses. Additionally, there was a greater (P < 0.05) percentage of consumers who indicated they would purchase unlabeled chops compared to labeled chops. These results, within the population sampled, indicate that carcass weight and chop thickness can affect consumer preference and thus should be considered by retailers when marketing fresh pork loin chops

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe