Kelin Xia, D Vijay Anand, Shikhar Saxena, Yuguang Mu
May 28, 2019·q-bio.QM·PDF Two types of osmolytes, i.e., trimethylamin N-oxide (TMAO) and urea, demonstrate dramatically different properties in a protein folding process. Even with the great progresses in revealing the potential underlying mechanism of these two osmolyte systems, many problems still remain unsolved. In this paper, we propose to use the persistent homology, a newly-invented topological method, to systematically study the osmolytes molecular aggregation and their hydrogen-bonding network from a global topological perspective. It has been found that, for the first time, TMAO and urea show two extremely different topological behaviors, i.e., extensive network and local cluster. In general, TMAO forms highly consistent large loop or circle structures in high concentrations. In contrast, urea is more tightly aggregated locally. Moreover, the resulting hydrogen-bonding networks also demonstrate distinguishable features. With the concentration increase, TMAO hydrogen-bonding networks vary greatly in their total number of loop structures and large-sized loop structures consistently increase. In contrast, urea hydrogen-bonding networks remain relatively stable with slight reduce of the total loop number. Moreover, the persistent entropy (PE) is, for the first time, used in characterization of the topological information of the aggregation and hydrogen-bonding networks. The average PE systematically increases with the concentration for both TMAO and urea, and decreases in their hydrogen-bonding networks. But their PE variances have totally different behaviors. Finally, topological features of the hydrogen-bonding networks are found to be highly consistent with those from the ion aggregation systems, indicating that our topological invariants can characterize intrinsic features of the "structure making" and "structure breaking" systems.
D. Vijay Anand, Moo K. Chung
Oct 15, 2021·q-bio.NC·PDF The closed loops or cycles in a brain network embeds higher order signal transmission paths, which provide fundamental insights into the functioning of the brain. In this work, we propose an efficient algorithm for systematic identification and modeling of cycles using persistent homology and the Hodge Laplacian. Various statistical inference procedures on cycles are developed. We validate the our methods on simulations and apply to brain networks obtained through the resting state functional magnetic resonance imaging. The computer codes for the Hodge Laplacian are given in https://github.com/laplcebeltrami/hodge.
D Vijay Anand, Kelin Xia, Yuguang Mu
Jul 14, 2019·q-bio.QM·PDF It has long been observed that trimethylamin N-oxide (TMAO) and urea demonstrate dramatically different properties in a protein folding process. Even with the enormous theoretical and experimental research work of the two osmolytes, various aspects of their underlying mechanisms still remain largely elusive. In this paper, we propose to use the weighted persistent homology to systematically study the osmolytes molecular aggregation and their hydrogen-bonding network from a local topological perspective. We consider two weighted models, i.e., localized persistent homology (LPH) and interactive persistent homology (IPH). From the localized persistent homology models, we have found that TMAO and urea have very different local topology. TMAO shows local network structures. With the concentration increase, the circle elements in these networks show a clear increase in their total numbers and a decrease in their relative sizes. In contrast, urea shows two types of local topological patterns, i.e., local clusters around 6 Å~ and a few global circle elements at around 12 Å. From the interactive persistent homology models, it has been found that our persistent radial distribution function (PRDF) from the global-scale IPH has same physical properties as the traditional radial distribution function (RDF). Moreover, PRDFs from the local-scale IPH can also be generated and used to characterize the local interaction information. Other than the clear difference of the first peak value of PRDFs at filtration size 4Å, TMAO and urea also shows very different behaviors at the second peak region from filtration size 5Å~ to 10 Å.
Zhenyu Meng, D Vijay Anand, Yunpeng Lu, Jie Wu, Kelin Xia
In this paper, we systematically review weighted persistent homology (WPH) models and their applications in biomolecular data analysis. Essentially, the weight value, which reflects physical, chemical and biological properties, can be assigned to vertices (atom centers), edges (bonds), or higher order simplexes (cluster of atoms), depending on the biomolecular structure, function, and dynamics properties. Further, we propose the first localized weighted persistent homology (LWPH). Inspired by the great success of element specific persistent homology (ESPH), we do not treat biomolecules as an inseparable system like all previous weighted models, instead we decompose them into a series of local domains, which may be overlapped with each other. The general persistent homology or weighted persistent homology analysis is then applied on each of these local domains. In this way, functional properties, that are embedded in local structures, can be revealed. Our model has been applied to systematically studying DNA structures. It has been found that our LWPH based features can be used to successfully discriminate the A-, B-, and Z-types of DNA. More importantly, our LWPH based PCA model can identify two configurational states of DNA structure in ion liquid environment, which can be revealed only by the complicated helical coordinate system. The great consistence with the helical-coordinate model demonstrates that our model captures local structure variations so well that it is comparable with geometric models. Moreover, geometric measurements are usually defined in very local regions. For instance, the helical-coordinate system is limited to one or two basepairs. However, our LWPH can quantitatively characterize structure information in local regions or domains with arbitrary sizes and shapes, where traditional geometrical measurements fail.
Soumya Das, D. Vijay Anand, Moo K. Chung
Understanding the common topological characteristics of the human brain network across a population is central to understanding brain functions. The abstraction of human connectome as a graph has been pivotal in gaining insights on the topological properties of the brain network. The development of group-level statistical inference procedures in brain graphs while accounting for the heterogeneity and randomness still remains a difficult task. In this study, we develop a robust statistical framework based on persistent homology using the order statistics for analyzing brain networks. The use of order statistics greatly simplifies the computation of the persistent barcodes. We validate the proposed methods using comprehensive simulation studies and subsequently apply to the resting-state functional magnetic resonance images. We found a statistically significant topological difference between the male and female brain networks.
D. Vijay Anand, Anass B El-Yaagoubi, Hernando Ombao, Moo K. Chung
Nov 19, 2022·q-bio.NC·PDF We propose to analyze dynamically changing brain networks by decomposing them into three orthogonal components through the Hodge decomposition. We propose to quantify the magnitude and relative strength of each component. We performed extensive simulation studies with known ground truth. The Hodge decomposition is then applied to the dynamically changing human brain networks obtained from a resting-state functional magnetic resonance imaging study. Our results indicate that the components of the Hodge decomposition contain biologically interpretable topological features that provide statistically significant findings not easily captured by traditional methods.
Yansong Liu, Ronnie Stafford, Pramit Khetrapal, Huriye Kocadag, Graça Carvalho, Patricia de Winter, Maryam Imran, Amelia Snook, Adamos Hadjivasiliou, D. Vijay Anand, Weining Lin, John Kelly, Yukun Zhou, Ivana Drobnjak
For patients undergoing systemic cancer therapy, the time between clinic visits is full of uncertainties and risks of unmonitored side effects. To bridge this gap in care, we developed and prospectively trialed a multi-modal AI framework for remote patient monitoring (RPM). This system integrates multi-modal data from the HALO-X platform, such as demographics, wearable sensors, daily surveys, and clinical events. Our observational trial is one of the largest of its kind and has collected over 2.1 million data points (6,080 patient-days) of monitoring from 84 patients. We developed and adapted a multi-modal AI model to handle the asynchronous and incomplete nature of real-world RPM data, forecasting a continuous risk of future adverse events. The model achieved an accuracy of 83.9% (AUROC=0.70). Notably, the model identified previous treatments, wellness check-ins, and daily maximum heart rate as key predictive features. A case study demonstrated the model's ability to provide early warnings by outputting escalating risk profiles prior to the event. This work establishes the feasibility of multi-modal AI RPM for cancer care and offers a path toward more proactive patient support.(Accepted at Europe NeurIPS 2025 Multimodal Representation Learning for Healthcare Workshop. Best Paper Poster Award.)
Moo K. Chung, D. Vijay Anand, Anass B El-Yaagoubi, Jae-Hun Jung, Anqi Qiu, Hernando Ombao
Apr 18, 2026·q-bio.NC·PDF Classical causal models, such as Granger causality and structural equation modeling, are largely restricted to acyclic interactions and struggle to represent cyclic and higher-order dynamics in complex networks. We introduce a causal framework grounded in a variational principle, interpreting causality as directional energy flow from high- to low-energy states along network connections. Using Hodge theory, network flows are decomposed into dissipative components and a persistent harmonic component that captures stable cyclic interactions. Applied to resting-state fMRI connectivity, our variational framework reveals robust cyclic causal patterns that are not detected by conventional causal models, highlighting the value of variational principles for causality.
Vinotha R, Hepsiba D, L. D. Vijay Anand, Deepak John Reji
Neural Text-to-speech (TTS) synthesis is a powerful technology that can generate speech using neural networks. One of the most remarkable features of TTS synthesis is its capability to produce speech in the voice of different speakers. This paper introduces voice cloning and speech synthesis https://pypi.org/project/voice-cloning/ an open-source python package for helping speech disorders to communicate more effectively as well as for professionals seeking to integrate voice cloning or speech synthesis capabilities into their projects. This package aims to generate synthetic speech that sounds like the natural voice of an individual, but it does not replace the natural human voice. The architecture of the system comprises a speaker verification system, a synthesizer, a vocoder, and noise reduction. Speaker verification system trained on a varied set of speakers to achieve optimal generalization performance without relying on transcriptions. Synthesizer is trained using both audio and transcriptions that generate Mel spectrogram from a text and vocoder which converts the generated Mel Spectrogram into corresponding audio signal. Then the audio signal is processed by a noise reduction algorithm to eliminate unwanted noise and enhance speech clarity. The performance of synthesized speech from seen and unseen speakers are then evaluated using subjective and objective evaluation such as Mean Opinion Score (MOS), Gross Pitch Error (GPE), and Spectral distortion (SD). The model can create speech in distinct voices by including speaker characteristics that are chosen randomly.