Large Language Models (LLMs) can be used as repositories of biological and chemical information to generate pharmacological lead compounds. However, for LLMs to focus on specific drug targets typically requires experimentation with progressively more refined prompts. Results thus become dependent not just on what is known about the target, but also on what is known about the prompt- engineering. In this paper, we separate the prompt into domain-constraints that can be written in a standard logical form and a simple text-based query. We investigate whether LLMs can be guided, not by refining prompts manually, but by refining the logical component automatically, keeping the query unchanged. We describe an iterative procedure LMLF (“Language Model with Logical Feedback”) in which the constraints are progressively refined using a logical notion of generalisation. On any iteration, newly generated instances are verified against the constraint, providing "logical-feedback" for the next iteration's refinement of the constraints. We evaluate LMLF using two well-known targets (inhibition of the Janus Kinase 2; and Dopamine Receptor D2); and two different LLMs (GPT-3 and PaLM). We show that LMLF, starting with the same logical constraints and query text, can be used to guide both LLMs to generate potential leads. We find: (a) Binding affinities of LMLF-generated molecules are skewed towards higher binding affinities than those from existing baselines; (b) LMLF results in generating molecules that are skewed towards higher binding affinities than without logical feedback; (c) Assessment by a computational chemist suggests that LMLF generated compounds may be novel inhibitors. These findings suggest that LLMs with logical feedback may provide a mechanism for generating new leads without requiring the domain-specialist to acquire sophisticated skills in prompt-engineering.

Deep neural network (DNN) models for retinopathy have estimated predictive accuracies in the mid-to-high 90%. However, the following aspects remain unaddressed: State-of-the-art models are complex and require substantial computational infrastructure to train and deploy; The reliability of predictions can vary widely. In this paper, we focus on these aspects and propose a form of iterative knowledge distillation (IKD), called IKD+ that incorporates a tradeoff between size, accuracy and reliability. We investigate the functioning of IKD+ using two widely used techniques for estimating model calibration (Platt-scaling and temperature-scaling), using the best-performing model available, which is an ensemble of EfficientNets with approximately 100M parameters. We demonstrate that IKD+ equipped with temperature-scaling results in models that show up to approximately 500-fold decreases in the number of parameters than the original ensemble without a significant loss in accuracy. In addition, calibration scores (reliability) for the IKD+ models are as good as or better than the base model.

Deep neural networks (DNNS) are prone to miscalibrated predictions, often exhibiting a mismatch between the predicted output and the associated confidence scores. Contemporary model calibration techniques mitigate the problem of overconfident predictions by pushing down the confidence of the winning class while increasing the confidence of the remaining classes across all test samples. However, from a deployment perspective an ideal model is desired to (i) generate well calibrated predictions for high-confidence samples with predicted probability say > 0.95 and (ii) generate a higher proportion of legitimate high-confidence samples. To this end, we propose a novel regularization technique that can be used with classification losses, leading to state-of-the-art calibrated predictions at test time; From a deployment standpoint in safety critical applications, only high-confidence samples from a well-calibrated model are of interest, as the remaining samples have to undergo manual inspection. Predictive confidence reduction of these potentially "high-confidence samples" is a downside of existing calibration approaches. We mitigate this via proposing a dynamic traintime data pruning strategy which prunes low confidence samples every few epochs, providing an increase in confident yet calibrated samples. We demonstrate state-of-the-art calibration performance across image classification benchmarks, reducing training time without much compromise in accuracy. We provide insights into why our dynamic pruning strategy that prunes low confidence training samples leads to an increase in high-confidence samples at test time.

We consider a class of visual analogical reasoning problems that involve discovering the sequence of transformations by which pairs of input/output images are related, so as to analogously transform future inputs. This program synthesis task can be easily solved via symbolic search. Using a variation of the ‘neural analogical reasoning’ approach, we instead search for a sequence of elementary neural network transformations that manipulate distributed representations derived from a symbolic space, to which input images are directly encoded. We evaluate the extent to which our ‘neural reasoning’ approach generalises for images with unseen shapes and positions.

Abstract In the area of neurocognition, classification of data is one of the most important phases. Conventional biologically inspired neural network models such as multilayer perceptrons (MLPs) are capable of learning and generalizing from exemplary patterns and are considered to be a popular choice for many different classification tasks. However, in the area of cognitive research, there lies a certain degree of uncertainty in acquired data. This uncertainty may be regarded as fuzziness. In this work, an attempt has been made to classify data which are associated with certain uncertainty. The resulting model is named as “FMLP.” Further, MLP sometimes suffers from local minima problem during the training phase. To overcome the problem of getting trapped in the local minima in error back propagation, three different population‐based evolutionary metaheuristics (genetic algorithm, particle swarm optimisation, and gravitational search) have been implemented for training the FMLP. The resulting models are evaluated for seven real‐world benchmark datasets, and it has been found that the implemented models could demonstrate exemplary performance for real‐world data classification problems under uncertainty.