AMPCliff: quantitative definition and benchmarking of activity cliffs in antimicrobial peptides

Activity cliff (AC) is a phenomenon that a pair of similar molecules differ by a small structural alternation but exhibit a large difference in their biochemical activities. The AC of small molecules has been extensively investigated but limited knowledge is accumulated about the AC phenomenon in peptides with canonical amino acids. This study introduces a quantitative definition and benchmarking framework AMPCliff for the AC phenomenon in antimicrobial peptides (AMPs) composed by canonical amino acids. A comprehensive analysis of the existing AMP dataset reveals a significant prevalence of AC within AMPs. AMPCliff quantifies the activities of AMPs by the metric minimum inhibitory concentration (MIC), and defines 0.9 as the minimum threshold for the normalized BLOSUM62 similarity score between a pair of aligned peptides with at least two-fold MIC changes. This study establishes a benchmark dataset of paired AMPs in Staphylococcus aureus from the publicly available AMP dataset GRAMPA, and conducts a rigorous procedure to evaluate various AMP AC prediction models, including nine machine learning, four deep learning algorithms, four masked language models, and four generative language models. Our analysis reveals that these models are capable of detecting AMP AC events and the pre-trained protein language ESM2 model demonstrates superior performance across the evaluations. The predictive performance of AMP activity cliffs remains to be further improved, considering that ESM2 with 33 layers only achieves the Spearman correlation coefficient=0.50 for the regression task of the MIC values on the benchmark dataset. Source code and additional resources are available at https://www.healthinformaticslab.org/supp/ or https://github.com/Kewei2023/AMPCliff-generation.

A Practical Survey on Zero-shot Prompt Design for In-context Learning

The remarkable advancements in large language models (LLMs) have brought about significant improvements in Natural Language Processing(NLP) tasks. This paper presents a comprehensive review of in-context learning techniques, focusing on different types of prompts, including discrete, continuous, few-shot, and zero-shot, and their impact on LLM performance. We explore various approaches to prompt design, such as manual design, optimization algorithms, and evaluation methods, to optimize LLM performance across diverse tasks. Our review covers key research studies in prompt engineering, discussing their methodologies and contributions to the field. We also delve into the challenges faced in evaluating prompt performance, given the absence of a single "best" prompt and the importance of considering multiple metrics. In conclusion, the paper highlights the critical role of prompt design in harnessing the full potential of LLMs and provides insights into the combination of manual design, optimization techniques, and rigorous evaluation for more effective and efficient use of LLMs in various NLP tasks.

Utilizing Large Language Models for Natural Interface to Pharmacology Databases

The drug development process necessitates that pharmacologists undertake various tasks, such as reviewing literature, formulating hypotheses, designing experiments, and interpreting results. Each stage requires accessing and querying vast amounts of information. In this abstract, we introduce a Large Language Model (LLM)-based Natural Language Interface designed to interact with structured information stored in databases. Our experiments demonstrate the feasibility and effectiveness of the proposed framework. This framework can generalize to query a wide range of pharmaceutical data and knowledge bases.

Self-Supervised Image Representation Learning: Transcending Masking with Paired Image Overlay

Self-supervised learning has become a popular approach in recent years for its ability to learn meaningful representations without the need for data annotation. This paper proposes a novel image augmentation technique, overlaying images, which has not been widely applied in self-supervised learning. This method is designed to provide better guidance for the model to understand underlying information, resulting in more useful representations. The proposed method is evaluated using contrastive learning, a widely used self-supervised learning method that has shown solid performance in downstream tasks. The results demonstrate the effectiveness of the proposed augmentation technique in improving the performance of self-supervised models.

Dynamic Portfolio Management with Reinforcement Learning

Dynamic Portfolio Management is a domain that concerns the continuous redistribution of assets within a portfolio to maximize the total return in a given period of time. With the recent advancement in machine learning and artificial intelligence, many efforts have been put in designing and discovering efficient algorithmic ways to manage the portfolio. This paper presents two different reinforcement learning agents, policy gradient actor-critic and evolution strategy. The performance of the two agents is compared during backtesting. We also discuss the problem set up from state space design, to state value function approximator and policy control design. We include the short position to give the agent more flexibility during assets redistribution and a constant trading cost of 0.25%. The agent is able to achieve 5% return in 10 days daily trading despite 0.25% trading cost.