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1. Model-based identification of conditionally-essential genes from transposon-insertion sequencing data

   https://doi.org/10.1371/journal.pcbi.1009273  

   Sarsani, Vishal; Aldikacti, Berent; He, Shai; Zeinert, Rilee; Chien, Peter; Flaherty, Patrick (March 2022, PLOS Computational Biology)

   Segata, Nicola (Ed.)

   The understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of genes under different environmental conditions. We propose a model-based method that uses regularized negative binomial regression to estimate the change in transposon insertions attributable to gene-environment changes in this genetic interaction study without transformations or uniform normalization. An empirical Bayes model for estimating the local false discovery rate combines unique and total count information to test for genes that show a statistically significant change in transposon counts. When applied to RB-TnSeq (randomized barcode transposon sequencing) and Tn-seq (transposon sequencing) libraries made in strains of Caulobacter crescentus using both total and unique count data the model was able to identify a set of conditionally beneficial or conditionally detrimental genes for each target condition that shed light on their functions and roles during various stress conditions. 

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2. Dynamic low-count PET image reconstruction using spatio-temporal primal dual network

   Hu R.; Cui J.; Li C.; Yu C.; Chen Y.; Liu H. (October 2023, Physics in medicine and biology)

   Objective. Dynamic positron emission tomography (PET) imaging, which can provide information on dynamic changes in physiological metabolism, is now widely used in clinical diagnosis and cancer treatment. However, the reconstruction from dynamic data is extremely challenging due to the limited counts received in individual frame, especially in ultra short frames. Recently, the unrolled modelbased deep learning methods have shown inspiring results for low-count PET image reconstruction with good interpretability. Nevertheless, the existing model-based deep learning methods mainly focus on the spatial correlations while ignore the temporal domain. Approach. In this paper, inspired by the learned primal dual (LPD) algorithm, we propose the spatio-temporal primal dual network (STPDnet) for dynamic low-count PET image reconstruction. Both spatial and temporal correlations are encoded by 3D convolution operators. The physical projection of PET is embedded in the iterative learning process of the network, which provides the physical constraints and enhances interpretability. Main results. The experiments of both simulation data and real rat scan data have shown that the proposed method can achieve substantial noise reduction in both temporal and spatial domains and outperform the maximum likelihood expectation maximization, spatio-temporal kernel method, LPD and FBPnet. Significance. Experimental results show STPDnet better reconstruction performance in the low count situation, which makes the proposed method particularly suitable in whole-body dynamic imaging and parametric PET imaging that require extreme short frames and usually suffer from high level of noise. 

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3. MIMO YOLO - A Multiple Input Multiple Output Model for Automatic Cell Counting

   https://doi.org/10.1109/CBMS58004.2023.00327  

   Morera, Hunter; Dave, Palak; Alahmari, Saeed; Kolinko, Yaroslav; Hall, Lawrence O.; Goldgof, Dmitry; Mouton, Peter R. (June 2023, 2023 IEEE 36th International Symposium)

   Across basic research studies, cell counting requires significant human time and expertise. Trained experts use thin focal plane scanning to count (click) cells in stained biological tissue. This computer-assisted process (optical disector) requires a well-trained human to select a unique best z-plane of focus for counting cells of interest. Though accurate, this approach typically requires an hour per case and is prone to inter-and intra-rater errors. Our group has previously proposed deep learning (DL)-based methods to automate these counts using cell segmentation at high magnification. Here we propose a novel You Only Look Once (YOLO) model that performs cell detection on multi-channel z-plane images (disector stack). This automated Multiple Input Multiple Output (MIMO) version of the optical disector method uses an entire z-stack of microscopy images as its input, and outputs cell detections (counts) with a bounding box of each cell and class corresponding to the z-plane where the cell appears in best focus. Compared to the previous segmentation methods, the proposed method does not require time-and labor-intensive ground truth segmentation masks for training, while producing comparable accuracy to current segmentation-based automatic counts. The MIMO-YOLO method was evaluated on systematic-random samples of NeuN-stained tissue sections through the neocortex of mouse brains (n=7). Using a cross validation scheme, this method showed the ability to correctly count total neuron numbers with accuracy close to human experts and with 100% repeatability (Test-Retest). 

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4. Near-Optimal Differentially Private Reinforcement Learning

   Qiao, Dan; Wang, Yu-Xiang (April 2023, Proceedings of Machine Learning Research)

   Ruiz, Francisco and (Ed.)

   Motivated by personalized healthcare and other applications involving sensitive data, we study online exploration in reinforcement learning with differential privacy (DP) constraints. Existing work on this problem established that no-regret learning is possible under joint differential privacy (JDP) and local differential privacy (LDP) but did not provide an algorithm with optimal regret. We close this gap for the JDP case by designing an $$\epsilon$$-JDP algorithm with a regret of $$\widetilde{O}(\sqrt{SAH^2T}+S^2AH^3/\epsilon)$$ which matches the information-theoretic lower bound of non-private learning for all choices of $$\epsilon> S^{1.5}A^{0.5} H^2/\sqrt{T}$$. In the above, $$S$$, $$A$$ denote the number of states and actions, $$H$$ denotes the planning horizon, and $$T$$ is the number of steps. To the best of our knowledge, this is the first private RL algorithm that achieves privacy for free asymptotically as $$T\rightarrow \infty$$. Our techniques — which could be of independent interest — include privately releasing Bernstein-type exploration bonuses and an improved method for releasing visitation statistics. The same techniques also imply a slightly improved regret bound for the LDP case. 

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5. Near-Optimal Differentially Private Reinforcement Learning

   Qiao, Dan; Wang, Yu-Xiang (April 2023, Proceedings of Machine Learning Research)

   Motivated by personalized healthcare and other applications involving sensitive data, we study online exploration in reinforcement learning with differential privacy (DP) constraints. Existing work on this problem established that no-regret learning is possible under joint differential privacy (JDP) and local differential privacy (LDP) but did not provide an algorithm with optimal regret. We close this gap for the JDP case by designing an ϵ-JDP algorithm with a regret of O˜(sqrt(SAH^2T) +S^2AH^3/ϵ) which matches the information-theoretic lower bound of non-private learning for all choices of ϵ>S^1.5A^0.5H^2/sqrt(T). In the above, S, A denote the number of states and actions, H denotes the planning horizon, and T is the number of steps. To the best of our knowledge, this is the first private RL algorithm that achieves \emph{privacy for free} asymptotically as T→∞. Our techniques -- which could be of independent interest -- include privately releasing Bernstein-type exploration bonuses and an improved method for releasing visitation statistics. The same techniques also imply a slightly improved regret bound for the LDP case. 

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