AMPGAN v2: Machine Learning-Guided Design of Antimicrobial Peptides.

Antibiotic resistance is a critical public health problem. Each year ∼2.8 million resistant infections lead to more than 35 000 deaths in the U.S. alone. Antimicrobial peptides (AMPs) show promise in treating resistant infections. However, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the development of AMP-based treatments, it is necessary to create design approaches with higher precision and selectivity toward resistant targets. Previously, we developed AMPGAN and obtained proof-of-concept evidence for the generative approach to design AMPs with experimental validation. Building on the success of AMPGAN, we present AMPGAN v2, a bidirectional conditional generative adversarial network (BiCGAN)-based approach for rational AMP design. AMPGAN v2 uses generator-discriminator dynamics to learn data-driven priors and controls generation using conditioning variables. The bidirectional component, implemented using a learned encoder to map data samples into the latent space of the generator, aids iterative manipulation of candidate peptides. These elements allow AMPGAN v2 to generate candidates that are novel, diverse, and tailored for specific applications, making it an efficient AMP design tool.

Augmenting Semantic Lexicons Using Word Embeddings and Transfer Learning.

Sentiment-aware intelligent systems are essential to a wide array of applications. These systems are driven by language models which broadly fall into two paradigms: Lexicon-based and contextual. Although recent contextual models are increasingly dominant, we still see demand for lexicon-based models because of their interpretability and ease of use. For example, lexicon-based models allow researchers to readily determine which words and phrases contribute most to a change in measured sentiment. A challenge for any lexicon-based approach is that the lexicon needs to be routinely expanded with new words and expressions. Here, we propose two models for automatic lexicon expansion. Our first model establishes a baseline employing a simple and shallow neural network initialized with pre-trained word embeddings using a non-contextual approach. Our second model improves upon our baseline, featuring a deep Transformer-based network that brings to bear word definitions to estimate their lexical polarity. Our evaluation shows that both models are able to score new words with a similar accuracy to reviewers from Amazon Mechanical Turk, but at a fraction of the cost.

Fragmentation and inefficiencies in US equity markets: Evidence from the Dow 30.

Using the most comprehensive source of commercially available data on the US National Market System, we analyze all quotes and trades associated with Dow 30 stocks in calendar year 2016 from the vantage point of a single and fixed frame of reference. We find that inefficiencies created in part by the fragmentation of the equity marketplace are relatively common and persist for longer than what physical constraints may suggest. Information feeds reported different prices for the same equity more than 120 million times, with almost 64 million dislocation segments featuring meaningfully longer duration and higher magnitude. During this period, roughly 22% of all trades occurred while the SIP and aggregated direct feeds were dislocated. The current market configuration resulted in a realized opportunity cost totaling over $160 million, a conservative estimate that does not take into account intra-day offsetting events.

Simon's fundamental rich-get-richer model entails a dominant first-mover advantage.

Herbert Simon's classic rich-get-richer model is one of the simplest empirically supported mechanisms capable of generating heavy-tail size distributions for complex systems. Simon argued analytically that a population of flavored elements growing by either adding a novel element or randomly replicating an existing one would afford a distribution of group sizes with a power-law tail. Here, we show that, in fact, Simon's model does not produce a simple power-law size distribution as the initial element has a dominant first-mover advantage, and will be overrepresented by a factor proportional to the inverse of the innovation probability. The first group's size discrepancy cannot be explained away as a transient of the model, and may therefore be many orders of magnitude greater than expected. We demonstrate how Simon's analysis was correct but incomplete, and expand our alternate analysis to quantify the variability of long term rankings for all groups. We find that the expected time for a first replication is infinite, and show how an incipient group must break the mechanism to improve their odds of success. We present an example of citation counts for a specific field that demonstrates a first-mover advantage consistent with our revised view of the rich-get-richer mechanism. Our findings call for a reexamination of preceding work invoking Simon's model and provide an expanded understanding going forward.