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In addition the new method gives a quantifiable level of confidence in each classification. AVAILABILITY The software can be found at https//github.com/bioarch-sjh/bacollite, and can be installed in R using devtools. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) 2020. Published by Oxford University Press.MOTIVATION Single-cell RNA-seq makes possible the investigation of variability in gene expression among cells, and dependence of variation on cell type. Statistical inference methods for such analyses must be scalable, and ideally interpretable. RESULTS We present an approach based on a modification of a recently published highly scalable variational autoencoder framework that provides interpretability without sacrificing much accuracy. We demonstrate that our approach enables identification of gene programs in massive datasets. Our strategy, namely the learning of factor models with the auto-encoding variational Bayes framework, is not domain specific and may be useful for other applications. AVAILABILITY The factor model is available in the scVI package hosted on https//github.com/YosefLab/scVI/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) 2020. Published by Oxford University Press.MOTIVATION High-throughput protein screening is a critical technique for dissecting and designing protein function. Libraries for these assays can be created through a number of means, including targeted or random mutagenesis of a template protein sequence or direct DNA synthesis. However, mutagenic library construction methods often yield vastly more non-functional than functional variants and, despite advances in large-scale DNA synthesis, individual synthesis of each desired DNA template is often prohibitively expensive. Consequently, many protein screening libraries rely on the use of degenerate codons (DCs), mixtures of DNA bases incorporated at specific positions during DNA synthesis, to generate highly diverse protein variant pools from only a few low-cost synthesis reactions. However, selecting DCs for sets of sequences that covary at multiple positions dramatically increases the difficulty of designing a DC library and leads to the creation of many undesired variants that can quickly outstrip screening capacity. RESULTS We introduce a novel algorithm for total DC library optimization, DeCoDe, based on integer linear programming. DeCoDe significantly outperforms state-of-the-art DC optimization algorithms and scales well to more than a hundred proteins sharing complex patterns of covariation (e.g., the lab-derived avGFP lineage). Moreover, DeCoDe is, to our knowledge, the first DC design algorithm with the capability to encode mixed-length protein libraries. We anticipate DeCoDe to be broadly useful for a variety of library generation problems, ranging from protein engineering attempts that leverage mutual information to the reconstruction of ancestral protein states. AVAILABILITY github.com/OrensteinLab/DeCoDe. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email [email protected] The purpose of this study was to analyze the clinical features of dome-shaped macula (DSM) in highly myopic eyes and its morphological relationship with myopic retinoschisis (MRS). Methods In this cross-sectional study, 409 eyes of 409 patients with high myopia who had spectral-domain optical coherence tomography (OCT) examinations were included. The associations of DSM with the distribution of MRS and ocular biometry were evaluated. Results Of 409 eyes, DSM was detected in 64 eyes (15.6%). The eyes with DSM were more myopic (-18.8 ± 3.9 vs. -13.4 ± 5.9; P less then 0.001) and had longer axial length (31.7 ± 2.4 vs. 29.5 ± 2.5; P less then 0.001) compared with those without DSM. A higher rate of extrafoveal retinoschisis (35.9% vs. 9.6%; P less then 0.001) and a lower rate of foveoschisis (10.9% vs. 26.1%; P = 0.01) were detected in the eyes with DSM compared with those without DSM. In the eyes with DSM, MRS was detected in 30 eyes (46.9%). MRS predominantly affected the extrafoveal area (76.7%), especially the base of the dome (82.6%). The extrafoveal retinoschisis was most frequently distributed in the superior quadrant (52.2%). None of the eyes with DSM displayed fovea-only retinoschisis. The ratio of the height and width of the macular bulge was higher in eyes with MRS than those without MRS (0.05 vs. 0.04; P = 0.001). Conclusions A DSM is found in highly myopic eyes with a longer axial length. Phenformin activator MRS in eyes with DSM is more likely to affect the extrafoveal area, especially the base of the dome. A steeper macular bulge is associated with the occurrence of MRS.Purpose The purpose of this study was to investigate the characteristics of focal γ-zone parapapillary atrophy (focal γPPA) in patients with primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT). Methods Three groups of POAG eyes (n = 214) were defined according to the circumferential extent of Bruch's membrane (BM) within the β-zone PPA, as follows (1) no γPPA (intact BM; n = 81), (2) conventional γPPA (γPPA involving the fovea-BM-opening axis; n = 89), and (3) focal γPPA (γPPA not involving the fovea-BM-opening axis; n = 44). Clinical and ocular characteristics, including age, axial length (AXL), and focal lamina cribrosa (LC) defects were compared among the three groups. Results The focal γPPA group was significantly older (60.6 ± 11.0 years) and had shorter AXL (24.10 ± 1.34 mm) than those of the conventional γPPA group (46.2 ± 13.8 years and 26.53 ± 1.61 mm, respectively; P less then 0.001). These values of the focal γPPA group were similar to those of the no γPPA group (23.73 ± 0.97 mm for AXL and 64.0 ± 13.0 years for age). The focal γPPA group had a significantly higher prevalence of focal LC defects than did the other two groups (70.5% [31/44] for the focal γPPA group versus 46.1% [41/89] for the conventional γPPA group versus 37.0% [30/81] for the no γPPA group; P = 0.002). Conclusions Focal γPPA was differentiated from conventional γPPA by older age and shorter AXL. Further, focal γPPA was frequently accompanied by focal LC defects. Longitudinal studies elucidating whether focal LC defects and focal γPPA share common pathogenesis are warranted.
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