Repeated cross-sectional time series single cell data confound several sources of variation, with contributions from measurement noise, stochastic cell-to-cell variation and cell progression at ...different rates. Time series from single cell assays are particularly susceptible to confounding as the measurements are not averaged over populations of cells. When several genes are assayed in parallel these effects can be estimated and corrected for under certain smoothness assumptions on cell progression.
We present a principled probabilistic model with a Bayesian inference scheme to analyse such data. We demonstrate our method's utility on public microarray, nCounter and RNA-seq datasets from three organisms. Our method almost perfectly recovers withheld capture times in an Arabidopsis dataset, it accurately estimates cell cycle peak times in a human prostate cancer cell line and it correctly identifies two precocious cells in a study of paracrine signalling in mouse dendritic cells. Furthermore, our method compares favourably with Monocle, a state-of-the-art technique. We also show using held-out data that uncertainty in the temporal dimension is a common confounder and should be accounted for in analyses of repeated cross-sectional time series.
Our method is available on CRAN in the DeLorean package.
john.reid@mrc-bsu.cam.ac.uk
Supplementary data are available at Bioinformatics online.
Field trials were conducted to assess the potential for stocking native unionid mussels in urban streams of the Chesapeake Bay catchment. Juvenile, hatchery‐raised mussels were placed in enclosures ...at five urban streams (two restored and three unrestored) and two nearby rural streams. Adult mussels were translocated to two restored urban streams. Mussel growth and survivorship were assessed at the stream sites and for individuals maintained at hatchery ponds.
At all sites, water quality conditions were generally suitable for mussels with respect to temperature, pH, and dissolved oxygen. Food resources, as indicated by the quantity and quality of suspended and benthic particulate matter, were higher among rural sites and lower in unrestored urban streams.
Positive growth rates were observed at all sites, among both juveniles (caged) and translocated adults. Mussel fatty acid profiles were generally similar among sites, except for docosahexaenoic acid (DHA), which was lower among stocked mussels relative to mussels maintained at the hatchery.
Among the unrestored urban streams, the frequent occurrence of high discharge events resulted in burial and downstream loss of enclosures. At restored urban streams and rural streams, the washout effects were less severe. Apart from washout effects, mortality, as indicated by the presence of dead mussels, was low (<10%).
Overall, rural and restored urban streams provided suitable conditions for stocking native mussels, whereas in unrestored urban streams, bed and bank instability during high discharge events resulted in a high attrition of mussels. Conservation efforts may be aided by the consideration of mussel habitat needs in the design of stream restoration projects. The inclusion of mussel stocking efforts in urban stream restoration projects has the potential to facilitate stream recovery, expand and bring greater attention to mussel conservation efforts, and garner public support for the preservation of stream health in urban areas.
Including contributions from leading scholars in the field from both Australia and North America, this collection explores diverse approaches to writing the lives of historians and ways of assessing ...the importance of doing so. Beginning with the writing of autobiographies by historians, the volume then turns to biographical studies, both of historians whose writings were in some sense nation-defining and those who may be regarded as having had a major influence on defining the discipline of history. The final section explores elements of collective biography, linking these to the formation of historical networks. A concluding essay by Barbara Caine offers a critical appraisal of the study of historians’ biographies and autobiographies to date, and maps out likely new directions for future work.
Purpose Controversy exists regarding the best method for creating the knee anterior cruciate ligament (ACL) femoral tunnel or socket. The purpose of this study was to systematically review the risks, ...benefits, advantages, and disadvantages of the endoscopic transtibial (TT) technique, anteromedial portal technique, outside-in technique, and outside-in retrograde drilling technique for creating the ACL femoral tunnel. Methods A PubMed search of English-language studies published between January 1, 2000, and February 17, 2014, was performed using the following keywords: “anterior cruciate ligament” AND “femoral tunnel.” Included were studies reporting risks, benefits, advantages, and/or disadvantages of any ACL femoral technique. In addition, references of included articles were reviewed to identify potential studies missed in the original search. Results A total of 27 articles were identified through the search. TT technique advantages include familiarity and proven long-term outcomes; disadvantages include the risk of nonanatomic placement because of constrained (TT) drilling. Anteromedial portal technique advantages include unconstrained anatomic placement; disadvantages include technical challenges, short tunnels or sockets, and posterior-wall blowout. Outside-in technique advantages include unconstrained anatomic placement; disadvantages include the need for 2 incisions. Retrograde drilling technique advantages include unconstrained anatomic placement, as well as all-epiphyseal drilling in skeletally immature patients; disadvantages include the need for fluoroscopy for all-epiphyseal drilling. Conclusions There is no one, single, established “gold-standard” technique for creation of the ACL femoral socket. Four accepted techniques show diverse and subjective advantages, disadvantages, risks, and benefits. Level of Evidence Level V, systematic review of Level II through V evidence.
Dynamic compression plating is a common type of fracture fixation used to compress between bone fragments. The quality of compression across the fracture is important for postoperative stability and ...primary bone healing. Compression quality may be affected by surgical variations in plate prebend, screw location, screw torque, fracture gap, and implant material. Computational modeling provides a tool for systematically examining these factors, and for visualizing the mechanisms involved. The purpose of this study was to develop a finite element model of dynamic compression plating that includes screw insertion under torque control, establish model credibility through sensitivity analyses and experimental validation, and use the model to examine the effects of surgical variables on fracture compression and postoperative stability. Model‐predicted compressive pressures had good agreement with corresponding synthetic bones experiments under a variety of conditions. Models demonstrated that introducing a 1.5 or 3 mm plate prebend (using a 4.5 mm narrow LCP plate) eliminated gapping at the far cortex, which is consistent with clinical recommendations. However, models also revealed that plate prebend led to sharp decreases in fracture compressive force, exceeding 80% in some cases. A 1.5 mm plate prebend resulted in the most uniform pressures across the fracture. Testing of a simplified model form used in previous computational modeling studies showed large inaccuracies for constructs with plate prebend. This study provides the first experimentally validated computational models of dynamic compression plate fracture fixation, and reveals important effects of plate prebend and fracture gap on fracture compression quality.
Integrative clustering is used to identify groups of samples by jointly analysing multiple datasets describing the same set of biological samples, such as gene expression, copy number, methylation ...etc. Most existing algorithms for integrative clustering assume that there is a shared consistent set of clusters across all datasets, and most of the data samples follow this structure. However in practice, the structure across heterogeneous datasets can be more varied, with clusters being joined in some datasets and separated in others. In this paper, we present a probabilistic clustering method to identify groups across datasets that do not share the same cluster structure. The proposed algorithm, Clusternomics, identifies groups of samples that share their global behaviour across heterogeneous datasets. The algorithm models clusters on the level of individual datasets, while also extracting global structure that arises from the local cluster assignments. Clusters on both the local and the global level are modelled using a hierarchical Dirichlet mixture model to identify structure on both levels. We evaluated the model both on simulated and on real-world datasets. The simulated data exemplifies datasets with varying degrees of common structure. In such a setting Clusternomics outperforms existing algorithms for integrative and consensus clustering. In a real-world application, we used the algorithm for cancer subtyping, identifying subtypes of cancer from heterogeneous datasets. We applied the algorithm to TCGA breast cancer dataset, integrating gene expression, miRNA expression, DNA methylation and proteomics. The algorithm extracted clinically meaningful clusters with significantly different survival probabilities. We also evaluated the algorithm on lung and kidney cancer TCGA datasets with high dimensionality, again showing clinically significant results and scalability of the algorithm.
Hidden Costs of Passive Restoration Zahawi, Rakan A; Reid, John L; Holl, Karen D
Restoration ecology,
20/May , Letnik:
22, Številka:
3
Journal Article
Recenzirano
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The first few years of tropical forest restoration can be expensive, especially when applied to expansive areas. In light of this, passive restoration has been recommended as a considerably cheaper ...or even free alternative. There are, however, both direct and indirect costs associated with passive restoration. First, the longer recovery time that is typically required in passive restoration can be perceived as project failure, especially when compared with nearby active restoration efforts. In the worst‐case scenario, this can lead to the premature termination of a project by a landowner who would like to see more rapid or visible results. Second, passive restoration may be viewed as land abandonment, and in developing nations where land tenure is not always strictly enforced this may invite unanticipated uses, such as ranchers who may unintentionally or intentionally allow livestock to take advantage of the “unused” forage grass, thus setting back recovery efforts. Lastly, passive restoration does have direct financial costs, including material costs for establishing fences and repairing them, and labor costs for site vigilance. These upfront investments may need to be made repeatedly in passive restoration efforts, and for a longer time period than for an active restoration project. Both the direct and indirect costs should be considered prior to choosing passive restoration as a strategy in a particular restoration project.
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The extracellular matrix (ECM) of tissues is an important mediator of cell function. Moreover, understanding cellular dynamics within their specific tissue context is also important ...for developmental biology, cancer research, and regenerative medicine. However, robust in vitro models that incorporate tissue-specific microenvironments are lacking. Here we describe a novel mammary-specific culture protocol that combines a self-gelling hydrogel comprised solely of ECM from decellularized rat or human breast tissue with the use of our previously described 3D bioprinting platform. We initially demonstrate that undigested and decellularized mammary tissue can support mammary epithelial and tumor cell growth. We then describe a methodology for generating mammary ECM extracts that can spontaneously gel to form hydrogels. These ECM hydrogels retain unique structural and signaling profiles that elicit differential responses when normal mammary and breast cancer cells are cultured within them. Using our bioprinter, we establish that we can generate large organoids/tumoroids in the all mammary-derived hydrogel. These findings demonstrate that our system allows for growth of organoids/tumoroids in a tissue-specific matrix with unique properties, thus providing a suitable platform for ECM and epithelial/cancer cell studies.
Factors within extracellular matrices (ECMs) are specific to their tissue of origin. It has been shown that tissue specific factors within the mammary gland’s ECM have pronounced effects on cellular differentiation and cancer behavior. Understanding the role of the ECM in controlling cell fate has major implications for developmental biology, tissue engineering, and cancer therapy. However, in vitro models to study cellular interactions with tissue specific ECM are lacking. Here we describe the generation of 3D hydrogels consisting solely of human or mouse mammary ECM. We demonstrate that these novel 3D culture substrates can sustain large 3D bioprinted organoid and tumoroid formation. This is the first demonstration of an all mammary ECM culture system capable of sustaining large structural growths.
Motif finding is a difficult problem that has been studied for over 20 years. Some older popular motif finders are not suitable for analysis of the large data sets generated by next-generation ...sequencing. We recently published an efficient approximation (STEME) to the EM algorithm that is at the core of many motif finders such as MEME. This approximation allows the EM algorithm to be applied to large data sets. In this work we describe several efficient extensions to STEME that are based on the MEME algorithm. Together with the original STEME EM approximation, these extensions make STEME a fully-fledged motif finder with similar properties to MEME. We discuss the difficulty of objectively comparing motif finders. We show that STEME performs comparably to existing prominent discriminative motif finders, DREME and Trawler, on 13 sets of transcription factor binding data in mouse ES cells. We demonstrate the ability of STEME to find long degenerate motifs which these discriminative motif finders do not find. As part of our method, we extend an earlier method due to Nagarajan et al. for the efficient calculation of motif E-values. STEME's source code is available under an open source license and STEME is available via a web interface.
Purpose The purpose of this study was to compare arthroscopic versus open examination of the proximal long head of the biceps tendon (LHB) in patients undergoing open, subpectoral tenodesis. Methods ...Eighty consecutive patients were prospectively enrolled, of whom 62 were included in the study. During arthroscopy, the most distal extent of the LHB visualized was marked with a Bovie device. The tendon was pulled into the joint with an arthroscopic grasper, showing additional LHB and was again marked with the device. LHB fraying, flattening, redness, and degeneration were graded as absent, mild, moderate, or severe. During open subpectoral tenodesis, the grossly visualized LHB was graded in the same manner and the locations of both marks plus the total length of the LHB observed during open visualization were measured and recorded. After subpectoral tenodesis, the excised portion of the LHB was histologically graded as normal, fibrosis/tendinosis, or inflamed. Results On average, during open tenodesis, 95 mm (range, 75 to 130 mm) of LHB was visualized. This was greater than the length visualized during diagnostic arthroscopy of 16 mm (range, 5 to 28 mm), or 17%, and the length visualized while pulling the tendon into the joint with an arthroscopic grasper of 30 mm (range, 15 to 45 mm), or 32%. The difference in LHB length observed during open versus arthroscopic examination with a grasper was statistically significant ( P < .0001). In addition, when compared with LHB pathology observed in an open manner, arthroscopic visualization showed only 67% of pathology, underestimated noted pathology in 56% of patients, and overestimated noted pathology in 11% of patients. Histologic evaluation showed fibrosis/tendinosis in 100% of cases but inflammation in only 5%. Conclusions When compared with open inspection during subpectoral tenodesis, arthroscopic examination of the LHB visualizes only 32% of the tendon and may underestimate pathology. Level of Evidence Level II, diagnostic study—development of diagnostic criteria based on consecutive patients with universally applied gold standard.
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