Lanthipeptide engineering: non-canonical amino acids, click chemistry and ring shuffling

Antimicrobial resistance is one of the greatest threats to global health nowadays and it has a significant impact on global health and economy throughout the world. Research and development for new technologies to combat antimicrobial resistance are urgently needed. Peptide-based therapeutics have gained greatly increased interest during recent years due to its high selectivity, efficacy, tolerability and excellent safety. Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent an important class of gene-coded peptides with extensive post-translational modifications. Among RiPPs, the class of lanthipeptides represents a rich source for promising leads against Gram-positive bacteria. The unique biosynthetic pathways and relatively low genetic complexity of biosynthesis make lantibiotics good candidates for synthetic biology and bioengineering to expand the antimicrobial arsenal. In this thesis, three different strategies: i) large-scale modular engineering aided by nanoFlaming screening, ii) incorporation of non-canonical amino acids, and iii) chemical coupling were employed to develop novel lantibiotic derivatives. These approaches are able to change the structure and chemical diversity of lanthipeptides and expanded our understanding of structure-activity relationship, and have also led to the development of lantibiotic derivatives with enhanced functionality in terms of activity spectrum, stability and specific activity against clinical relevant antibiotic-resistant pathogens

TLGP: a flexible transfer learning algorithm for gene prioritization based on heterogeneous source domain

BackgroundGene prioritization (gene ranking) aims to obtain the centrality of genes, which is critical for cancer diagnosis and therapy since keys genes correspond to the biomarkers or targets of drugs. Great efforts have been devoted to the gene ranking problem by exploring the similarity between candidate and known disease-causing genes. However, when the number of disease-causing genes is limited, they are not applicable largely due to the low accuracy. Actually, the number of disease-causing genes for cancers, particularly for these rare cancers, are really limited. Therefore, there is a critical needed to design effective and efficient algorithms for gene ranking with limited prior disease-causing genes.ResultsIn this study, we propose a transfer learning based algorithm for gene prioritization (called TLGP) in the cancer (target domain) without disease-causing genes by transferring knowledge from other cancers (source domain). The underlying assumption is that knowledge shared by similar cancers improves the accuracy of gene prioritization. Specifically, TLGP first quantifies the similarity between the target and source domain by calculating the affinity matrix for genes. Then, TLGP automatically learns a fusion network for the target cancer by fusing affinity matrix, pathogenic genes and genomic data of source cancers. Finally, genes in the target cancer are prioritized. The experimental results indicate that the learnt fusion network is more reliable than gene co-expression network, implying that transferring knowledge from other cancers improves the accuracy of network construction. Moreover, TLGP outperforms state-of-the-art approaches in terms of accuracy, improving at least 5%.ConclusionThe proposed model and method provide an effective and efficient strategy for gene ranking by integrating genomic data from various cancers

A survey on vulnerability of federated learning: A learning algorithm perspective

Federated Learning (FL) has emerged as a powerful paradigm for training Machine Learning (ML), particularly Deep Learning (DL) models on multiple devices or servers while maintaining data localized at owners’ sites. Without centralizing data, FL holds promise for scenarios where data integrity, privacy and security and are critical. However, this decentralized training process also opens up new avenues for opponents to launch unique attacks, where it has been becoming an urgent need to understand the vulnerabilities and corresponding defense mechanisms from a learning algorithm perspective. This review paper takes a comprehensive look at malicious attacks against FL, categorizing them from new perspectives on attack origins and targets, and providing insights into their methodology and impact. In this survey, we focus on threat models targeting the learning process of FL systems. Based on the source and target of the attack, we categorize existing threat models into four types, Data to Model (D2M), Model to Data (M2D), Model to Model (M2M) and composite attacks. For each attack type, we discuss the defense strategies proposed, highlighting their effectiveness, assumptions and potential areas for improvement. Defense strategies have evolved from using a singular metric to excluding malicious clients, to employing a multifaceted approach examining client models at various phases. In this survey paper, our research indicates that the to-learn data, the learning gradients, and the learned model at different stages all can be manipulated to initiate malicious attacks that range from undermining model performance, reconstructing private local data, and to inserting backdoors. We have also seen these threat are becoming more insidious. While earlier studies typically amplified malicious gradients, recent endeavors subtly alter the least significant weights in local models to bypass defense measures. This literature review provides a holistic understanding of the current FL threat landscape and highlights the importance of developing robust, efficient, and privacy-preserving defenses to ensure the safe and trusted adoption of FL in real-world applications. The categorized bibliography can be found at: https://github.com/Rand2AI/Awesome-Vulnerability-of-Federated-Learning

3D interactive coronary artery segmentation using random forests and Markov random field optimization

Coronary artery segmentation plays a vital important role in coronary disease diagnosis and treatment. In this paper, we present a machine learning based interactive coronary artery segmentation method for 3D computed tomography angiography images. We first apply vessel diffusion to reduce noise interference and enhance the tubular structures in the images. A few user strokes are required to specify region of interest and background. Various image features for detecting the coronary arteries are then extracted in a multi-scale fashion, and are fed into a random forests classifier, which assigns each voxel with probability values of being coronary artery and background. The final segmentation is carried through an MRF based optimization using primal dual algorithm. A connectivity component analysis is carried out as post processing to remove isolated, small regions to produce the segmented coronary arterial vessels. The proposed method requires limited user interference and achieves robust segmentation results

Age-Related Macular Degeneration Detection and Stage Classification Using Choroidal OCT Images

In this paper, we propose a machine learning based method to detect AMD and distinguish the di↵erent stages using choroidal images obtained from optical coherence tomography (OCT). We extract texture features using a Gabor filter bank and non-linear energy transformation. Then the histogram based feature descriptors are used to train the random forests, Support Vector Machine (SVM) and neural networks, which are tested on our choroid OCT image dataset with 21 participants

A bag of words approach to subject specific 3D human pose interaction classification with random decision forests

In this work, we investigate whether it is possible to distinguish conversational interactions from observing human motion alone, in particular subject specific gestures in 3D. We adopt Kinect sensors to obtain 3D displacement and velocity measurements, followed by wavelet decomposition to extract low level temporal features. These features are thengeneralized to form a visual vocabulary that can be further generalized to a set of topics from temporal distributions of visual vocabulary. A subject specific supervised learning approach based on Random Forests is used to classify the testing sequences to seven different conversational scenarios. These conversational scenarios concerned in this workhave rather subtle differences among them. Unlike typical action or event recognition, each interaction in our case contain many instances of primitive motions and actions, many of which are shared among different conversation scenarios. That is the interactions we are concerned with are not micro or instant events, such as hugging and high-five, but rather interactions over a period of time that consists rather similar individual motions, micro actions and interactions. We believe this is among one of the first work that is devoted to subject specific conversational interaction classification using 3D pose features and to show this task is indeed possible