Multimodal Machine Learning Combining Facial Images and Clinical Texts Improves Diagnosis of Rare Genetic Diseases

Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible answer over a prolonged period of multiple years. Addressing this diagnostic odyssey thus have substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features, which can be used by artificial intelligence algorithms to facilitate clinical diagnosis, in prioritizing candidate diseases to be further examined by lab tests or genetic assays, or in helping the phenotype-driven reinterpretation of genome/exome sequencing data. However, existing methods using frontal facial photo were built on conventional Convolutional Neural Networks (CNNs), rely exclusively on facial images, and cannot capture non-facial phenotypic traits and demographic information essential for guiding accurate diagnoses. Here we introduce GestaltMML, a multimodal machine learning (MML) approach solely based on the Transformer architecture. It integrates the facial images, demographic information (age, sex, ethnicity), and clinical notes of patients to improve prediction accuracy. Furthermore, we also introduce GestaltGPT, a GPT-based methodology with few-short learning capacities that exclusively harnesses textual inputs using a range of large language models (LLMs) including Llama 2, GPT-J and Falcon. We evaluated these methods on a diverse range of datasets, including 449 diseases from the GestaltMatcher Database, several in-house datasets on Beckwith-Wiedemann syndrome, Sotos syndrome, NAA10-related syndrome (neurodevelopmental syndrome) and others. Our results suggest that GestaltMML/GestaltGPT effectively incorporate multiple modalities of data, greatly narrow down candidate genetic diagnosis of rare diseases, and may facilitate the reinterpretation of genome/exome sequencing data.

Not All Large Language Models Succumb to the "Reversal Curse": A Comparative Study of Deductive Logical Reasoning in BERT and GPT Models

The "Reversal Curse" refers to the scenario where auto-regressive decoder large language models (LLMs), such as ChatGPT, trained on "A is B" fail to learn "B is A", demonstrating a basic failure of logical deduction. This raises a red flag in the use of GPT models for certain general tasks such as constructing knowledge graphs, considering their adherence to this symmetric principle. In our study, we examined a bidirectional LLM, BERT, and found that it is immune to the reversal curse. Driven by ongoing efforts to construct biomedical knowledge graphs with LLMs, we also embarked on evaluating more complex but essential deductive reasoning capabilities. This process included first training encoder and decoder language models to master the intersection ($\cap$) and union ($\cup$) operations on two sets and then moving on to assess their capability to infer different combinations of union ($\cup$) and intersection ($\cap$) operations on three newly created sets. The findings showed that while both encoder and decoder language models, trained for tasks involving two sets (union/intersection), were proficient in such scenarios, they encountered difficulties when dealing with operations that included three sets (various combinations of union and intersection). Our research highlights the distinct characteristics of encoder and decoder models in simple and complex logical reasoning. In practice, the choice between BERT and GPT should be guided by the specific requirements and nature of the task at hand, leveraging their respective strengths in bidirectional context comprehension and sequence prediction.

Enhancing Phenotype Recognition in Clinical Notes Using Large Language Models: PhenoBCBERT and PhenoGPT

We hypothesize that large language models (LLMs) based on the transformer architecture can enable automated detection of clinical phenotype terms, including terms not documented in the HPO. In this study, we developed two types of models: PhenoBCBERT, a BERT-based model, utilizing Bio+Clinical BERT as its pre-trained model, and PhenoGPT, a GPT-based model that can be initialized from diverse GPT models, including open-source versions such as GPT-J, Falcon, and LLaMA, as well as closed-source versions such as GPT-3 and GPT-3.5. We compared our methods with PhenoTagger, a recently developed HPO recognition tool that combines rule-based and deep learning methods. We found that our methods can extract more phenotype concepts, including novel ones not characterized by HPO. We also performed case studies on biomedical literature to illustrate how new phenotype information can be recognized and extracted. We compared current BERT-based versus GPT-based models for phenotype tagging, in multiple aspects including model architecture, memory usage, speed, accuracy, and privacy protection. We also discussed the addition of a negation step and an HPO normalization layer to the transformer models for improved HPO term tagging. In conclusion, PhenoBCBERT and PhenoGPT enable the automated discovery of phenotype terms from clinical notes and biomedical literature, facilitating automated downstream tasks to derive new biological insights on human diseases.

Deep Reinforcement Learning Empowered Rate Selection of XP-HARQ

The complex transmission mechanism of cross-packet hybrid automatic repeat request (XP-HARQ) hinders its optimal system design. To overcome this difficulty, this letter attempts to use the deep reinforcement learning (DRL) to solve the rate selection problem of XP-HARQ over correlated fading channels. In particular, the long term average throughput (LTAT) is maximized by properly choosing the incremental information rate for each HARQ round on the basis of the outdated channel state information (CSI) available at the transmitter. The rate selection problem is first converted into a Markov decision process (MDP), which is then solved by capitalizing on the algorithm of deep deterministic policy gradient (DDPG) with prioritized experience replay. The simulation results finally corroborate the superiority of the proposed XP-HARQ scheme over the conventional HARQ with incremental redundancy (HARQ-IR) and the XP-HARQ with only statistical CSI.

On the Prime Number Divisibility by Deep Learning

Certain tasks such as determining whether a given integer can be divided by 2, 3, or other prime numbers may be trivial for human beings, but can be less straightforward for computers in the absence of pre-specified algorithms. In this paper, we tested multiple deep learning architectures and feature engineering approaches, and evaluated the scenario of determining divisibility of large finite integers (up to $2^{32}$) by small prime numbers. It turns out that, regardless of the network frameworks or the complexity of the network structures (CNN, RNN, Transformer, etc.), the ability to predict the prime number divisibility critically depends on the feature space fed into the deep learning models. We also evaluated commercially available Automated Machine Learning (AutoML) pipelines from Amazon, Google and Microsoft, and demonstrated that they failed to address this issue unless appropriately engineered features were provided. We further proposed a closed form solution to the problem using the ordinary linear regression on Fourier series basis vectors, and showed its success. Finally, we evaluated prompt-based learning using ChatGPT and demonstrated its success on small primes and apparent failures on larger primes. We conclude that feature engineering remains an important task to improve the performance, increase the interpretability, and reduce the complexity of machine learning/deep learning models, even in the era of AutoML and large-language models (LLMs).