arXiv subjects

Bud Mishra

Publications and source records attributed to Bud Mishra.

At least 19 recordsLinked to original sources

arXiv2026

Control Laws in Aging and Longevity: A Control Theory of Aging for Gerotherapeutic Drug Discovery

Existing aging theories describe what changes with age but do not prescribe how to intervene. We propose a control-theoretic framework that is not merely descriptive but prescriptive: it specifies which intervention, at which dose and sequence, under which safety constraints, will restore a measured biological state to a functional region. Aging is defined as progressive loss of safe controllability; biological age is the minimum safe control cost of functional restoration. Drugs are modeled as vector fields on biological state space whose non-commutativity, quantified by Lie brackets, predicts that intervention order determines outcome. The core differentiation from prior theories is operational: the framework outputs ranked targets, optimal sequences, safety-constrained protocols, and falsifiable predictions directly usable in drug discovery, rather than mechanistic ontologies or correlative biomarkers. We present a five-dimensional ODE model with analytic Lie-bracket derivation, a modality-aware control layer, three translational case studies, an implementation architecture with power analysis, and empirical scoring of aging interventions across five biological epochs. Twenty falsifiable predictions are enumerated. The central claim is that control-value reduction predicts translational success better than Hallmark annotation or biomarker reversal alone. If validated, this provides the missing interventional layer connecting aging biology to rational gerotherapeutic discovery.

q-bio.MN↗

arXiv2026

Adversarial Data Modeling in Epidemiology

Epidemiological models increasingly rely on crowdsourced, self-reported behavioral data such as vaccination status, mask usage, and social distancing adherence. This data, however, is not passively sampled but instead strategically reported, making it a canonical case of adversarial input to a data mining pipeline. Individuals misreport for various reasons, e.g., to avoid penalties, to access benefits, or to express distrust in public health authorities. We introduce a data-modeling framework that casts the interaction between the population and a public health authority as a signaling game. This approach provides both a generative model of strategically-corrupted behavioral data and a mechanism for the receiver to recover reliable signal from it. Individuals (senders) choose how to report their behaviors, while the public health authority (receiver) updates their epidemiological model(s) based on potentially distorted signals, and modifies its trust in incoming reports accordingly. Focusing on deception around masking and vaccination, we characterize analytically game equilibrium outcomes as distinct regimes of data corruption, and evaluate the degree to which deception can be tolerated while maintaining epidemic control through policy interventions. In large scale simulations, our results show that even under pervasive dishonesty in pooling equilibria, well-designed sender and receiver strategies can still maintain effective epidemic control. Real-world validation further shows that behavioral distortions often exhibit structured patterns rather than arbitrary noise. This work advances the understanding of adversarial data in epidemiology and offers tools for designing more robust public health models in the presence of strategic user behavior.

cs.GT↗

arXiv2021

Testing the efficacy of epidemic testing

The cataclysmic contagion based calamity -- Covid-19 has shown us a clear need for a comprehensive community based strategy that overcomes the sheer complexity of controlling it and the caveats of current methods. In this regard, as seen in earlier epidemics, testing has always been an integral part of containment policy. But one has to consider the optimality of a testing scheme based on the resultant disease spread in the community and not based on purely increasing testing efficiency. Therefore, taking a decision is no easy feat and must consider the community utility constrained by its priorities, budget, risks, collateral and abilities which can be encoded into the optimization of the strategy. We thus propose a simple pooling strategy that is easy to customize and practical to implement, unlike other complex and computationally intensive methods.

physics.soc-ph↗

arXiv2021

Efficient Evolutionary Models with Digraphons

We present two main contributions which help us in leveraging the theory of graphons for modeling evolutionary processes. We show a generative model for digraphons using a finite basis of subgraphs, which is representative of biological networks with evolution by duplication. We show a simple MAP estimate on the Bayesian non parametric model using the Dirichlet Chinese restaurant process representation, with the help of a Gibbs sampling algorithm to infer the prior. Next we show an efficient implementation to do simulations on finite basis segmentations of digraphons. This implementation is used for developing fast evolutionary simulations with the help of an efficient 2-D representation of the digraphon using dynamic segment-trees with the square-root decomposition representation. We further show how this representation is flexible enough to handle changing graph nodes and can be used to also model dynamic digraphons with the help of an amortized update representation to achieve an efficient time complexity of the update at $O(\sqrt{|V|}\log{|V|})$.

cs.LG↗

arXiv2021

To mock a Mocking bird : Studies in Biomimicry

This paper dwells on certain novel game-theoretic investigations in bio-mimicry, discussed from the perspectives of information asymmetry, individual utility and its optimization via strategic interactions involving co-evolving preys (e.g., insects) and predators (e.g., reptiles) who learn. Formally, we consider a panmictic ecosystem, occupied by species of prey with relatively short lifespan, which evolve mimicry signals over generations as they interact with predators with relatively longer lifespans, thus endowing predators with the ability to learn prey signals. Every prey sends a signal and provides utility to the predator. The prey can be either nutritious or toxic to the predator, but the prey may signal (possibly) deceptively without revealing its true "type." The model is used to study the situation where multi-armed bandit predators with zero prior information are introduced into the ecosystem. As a result of exploration and exploitation the predators naturally select the prey that result in the evolution of those signals. This co-evolution of strategies produces a variety of interesting phenomena which are subjects of this paper.

q-bio.PE↗

arXiv2021

Creolizing the Web

The evolution of language has been a hotly debated subject with contradicting hypotheses and unreliable claims. Drawing from signalling games, dynamic population mechanics, machine learning and algebraic topology, we present a method for detecting evolutionary patterns in a sociological model of language evolution. We develop a minimalistic model that provides a rigorous base for any generalized evolutionary model for language based on communication between individuals. We also discuss theoretical guarantees of this model, ranging from stability of language representations to fast convergence of language by temporal communication and language drift in an interactive setting. Further we present empirical results and their interpretations on a real world dataset from \rdt to identify communities and echo chambers for opinions, thus placing obstructions to reliable communication among communities.

cs.CL↗

arXiv2018

Origin of Biomolecular Networks

Biomolecular networks have already found great utility in characterizing complex biological systems arising from pair-wise interactions amongst biomolecules. Here, we review how graph theoretical approaches can be applied not only for a better understanding of various proximate (mechanistic) relations, but also, ultimate (evolutionary) structures encoded in such networks. A central question deals with the evolutionary dynamics by which different topologies of biomolecular networks might have evolved, as well as the biological principles that can be hypothesized from a deeper understanding of the induced network dynamics. We emphasize the role of gene duplication in terms of signaling game theory, whereby sender and receiver gene players accrue benefit from gene duplication, leading to a preferential attachment mode of network growth. Information asymmetry between sender and receiver genes is hypothesized as a key driver of the resulting network topology. The study of the resulting dynamics suggests many mathematical/computational problems, the majority of which are intractable but yield to efficient approximation algorithms, when studied through an algebraic graph theoretic lens.

q-bio.MN↗

arXiv2018

Decidability in Robot Manipulation Planning

Consider the problem of planning collision-free motion of $n$ objects in the plane movable through contact with a robot that can autonomously translate in the plane and that can move a maximum of $m \leq n$ objects simultaneously. This represents the abstract formulation of a manipulation planning problem that is proven to be decidable in this paper. The tools used for proving decidability of this simplified manipulation planning problem are, in fact, general enough to handle the decidability problem for the wider class of systems characterized by a stratified configuration space. These include, for example, problems of legged and multi-contact locomotion, bi-manual manipulation. In addition, the described approach does not restrict the dynamics of the manipulation system to be considered.

cs.RO↗

arXiv2018

Probabilistic Causal Analysis of Social Influence

Mastering the dynamics of social influence requires separating, in a database of information propagation traces, the genuine causal processes from temporal correlation, i.e., homophily and other spurious causes. However, most studies to characterize social influence, and, in general, most data-science analyses focus on correlations, statistical independence, or conditional independence. Only recently, there has been a resurgence of interest in "causal data science", e.g., grounded on causality theories. In this paper we adopt a principled causal approach to the analysis of social influence from information-propagation data, rooted in the theory of probabilistic causation. Our approach consists of two phases. In the first one, in order to avoid the pitfalls of misinterpreting causation when the data spans a mixture of several subtypes ("Simpson's paradox"), we partition the set of propagation traces into groups, in such a way that each group is as less contradictory as possible in terms of the hierarchical structure of information propagation. To achieve this goal, we borrow the notion of "agony" and define the Agony-bounded Partitioning problem, which we prove being hard, and for which we develop two efficient algorithms with approximation guarantees. In the second phase, for each group from the first phase, we apply a constrained MLE approach to ultimately learn a minimal causal topology. Experiments on synthetic data show that our method is able to retrieve the genuine causal arcs w.r.t. a ground-truth generative model. Experiments on real data show that, by focusing only on the extracted causal structures instead of the whole social graph, the effectiveness of predicting influence spread is significantly improved.

cs.SI↗

arXiv2018

Causal Data Science for Financial Stress Testing

The most recent financial upheavals have cast doubt on the adequacy of some of the conventional quantitative risk management strategies, such as VaR (Value at Risk), in many common situations. Consequently, there has been an increasing need for verisimilar financial stress testings, namely simulating and analyzing financial portfolios in extreme, albeit rare scenarios. Unlike conventional risk management which exploits statistical correlations among financial instruments, here we focus our analysis on the notion of probabilistic causation, which is embodied by Suppes-Bayes Causal Networks (SBCNs); SBCNs are probabilistic graphical models that have many attractive features in terms of more accurate causal analysis for generating financial stress scenarios. In this paper, we present a novel approach for conducting stress testing of financial portfolios based on SBCNs in combination with classical machine learning classification tools. The resulting method is shown to be capable of correctly discovering the causal relationships among financial factors that affect the portfolios and thus, simulating stress testing scenarios with a higher accuracy and lower computational complexity than conventional Monte Carlo Simulations.

cs.LG↗

arXiv2017

Exposing the Probabilistic Causal Structure of Discrimination

Discrimination discovery from data is an important task aiming at identifying patterns of illegal and unethical discriminatory activities against protected-by-law groups, e.g., ethnic minorities. While any legally-valid proof of discrimination requires evidence of causality, the state-of-the-art methods are essentially correlation-based, albeit, as it is well known, correlation does not imply causation. In this paper we take a principled causal approach to the data mining problem of discrimination detection in databases. Following Suppes' probabilistic causation theory, we define a method to extract, from a dataset of historical decision records, the causal structures existing among the attributes in the data. The result is a type of constrained Bayesian network, which we dub Suppes-Bayes Causal Network (SBCN). Next, we develop a toolkit of methods based on random walks on top of the SBCN, addressing different anti-discrimination legal concepts, such as direct and indirect discrimination, group and individual discrimination, genuine requirement, and favoritism. Our experiments on real-world datasets confirm the inferential power of our approach in all these different tasks.

cs.DB↗

arXiv2017

Algorithmic Methods to Infer the Evolutionary Trajectories in Cancer Progression

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next generation sequencing (NGS) data, and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent works on "selective advantage" relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications as it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations and progression model inference. We demonstrate PiCnIc's ability to reproduce much of the current knowledge on colorectal cancer progression, as well as to suggest novel experimentally verifiable hypotheses.

q-bio.GN↗

arXiv2016

TRONCO: an R package for the inference of cancer progression models from heterogeneous genomic data

Motivation: We introduce TRONCO (TRanslational ONCOlogy), an open-source R package that implements the state-of-the-art algorithms for the inference of cancer progression models from (epi)genomic mutational profiles. TRONCO can be used to extract population-level models describing the trends of accumulation of alterations in a cohort of cross-sectional samples, e.g., retrieved from publicly available databases, and individual-level models that reveal the clonal evolutionary history in single cancer patients, when multiple samples, e.g., multiple biopsies or single-cell sequencing data, are available. The resulting models can provide key hints in uncovering the evolutionary trajectories of cancer, especially for precision medicine or personalized therapy. Availability: TRONCO is released under the GPL license, it is hosted in the Software section at http://bimib.disco.unimib.it/ and archived also at bioconductor.org. Contact: tronco@disco.unimib.it

q-bio.QM↗

arXiv2015

CAPRI: Efficient Inference of Cancer Progression Models from Cross-sectional Data

We devise a novel inference algorithm to effectively solve the cancer progression model reconstruction problem. Our empirical analysis of the accuracy and convergence rate of our algorithm, CAncer PRogression Inference (CAPRI), shows that it outperforms the state-of-the-art algorithms addressing similar problems. Motivation: Several cancer-related genomic data have become available (e.g., The Cancer Genome Atlas, TCGA) typically involving hundreds of patients. At present, most of these data are aggregated in a cross-sectional fashion providing all measurements at the time of diagnosis.Our goal is to infer cancer progression models from such data. These models are represented as directed acyclic graphs (DAGs) of collections of selectivity relations, where a mutation in a gene A selects for a later mutation in a gene B. Gaining insight into the structure of such progressions has the potential to improve both the stratification of patients and personalized therapy choices. Results: The CAPRI algorithm relies on a scoring method based on a probabilistic theory developed by Suppes, coupled with bootstrap and maximum likelihood inference. The resulting algorithm is efficient, achieves high accuracy, and has good complexity, also, in terms of convergence properties. CAPRI performs especially well in the presence of noise in the data, and with limited sample sizes. Moreover CAPRI, in contrast to other approaches, robustly reconstructs different types of confluent trajectories despite irregularities in the data.We also report on an ongoing investigation using CAPRI to study atypical Chronic Myeloid Leukemia, in which we uncovered non trivial selectivity relations and exclusivity patterns among key genomic events.

math.ST↗

arXiv2014

Inferring tree causal models of cancer progression with probability raising

Existing techniques to reconstruct tree models of progression for accumulative processes, such as cancer, seek to estimate causation by combining correlation and a frequentist notion of temporal priority. In this paper, we define a novel theoretical framework called CAPRESE (CAncer PRogression Extraction with Single Edges) to reconstruct such models based on the notion of probabilistic causation defined by Suppes. We consider a general reconstruction setting complicated by the presence of noise in the data due to biological variation, as well as experimental or measurement errors. To improve tolerance to noise we define and use a shrinkage-like estimator. We prove the correctness of our algorithm by showing asymptotic convergence to the correct tree under mild constraints on the level of noise. Moreover, on synthetic data, we show that our approach outperforms the state-of-the-art, that it is efficient even with a relatively small number of samples and that its performance quickly converges to its asymptote as the number of samples increases. For real cancer datasets obtained with different technologies, we highlight biologically significant differences in the progressions inferred with respect to other competing techniques and we also show how to validate conjectured biological relations with progression models.

math.ST↗

arXiv2012

Reevaluating Assembly Evaluations with Feature Response Curves: GAGE and Assemblathons

In just the last decade, a multitude of bio-technologies and software pipelines have emerged to revolutionize genomics. To further their central goal, they aim to accelerate and improve the quality of de novo whole-genome assembly starting from short DNA reads. However, the performance of each of these tools is contingent on the length and quality of the sequencing data, the structure and complexity of the genome sequence, and the resolution and quality of long-range information. Furthermore, in the absence of any metric that captures the most fundamental "features" of a high-quality assembly, there is no obvious recipe for users to select the most desirable assembler/assembly. International competitions such as Assemblathons or GAGE tried to identify the best assembler(s) and their features. Some what circuitously, the only available approach to gauge de novo assemblies and assemblers relies solely on the availability of a high-quality fully assembled reference genome sequence. Still worse, reference-guided evaluations are often both difficult to analyze, leading to conclusions that are difficult to interpret. In this paper, we circumvent many of these issues by relying upon a tool, dubbed FRCbam, which is capable of evaluating de novo assemblies from the read-layouts even when no reference exists. We extend the FRCurve approach to cases where lay-out information may have been obscured, as is true in many deBruijn-graph-based algorithms. As a by-product, FRCurve now expands its applicability to a much wider class of assemblers -- thus, identifying higher-quality members of this group, their inter-relations as well as sensitivity to carefully selected features, with or without the support of a reference sequence or layout for the reads. The paper concludes by reevaluating several recently conducted assembly competitions and the datasets that have resulted from them.

q-bio.GN↗

arXiv2012

Towards Cancer Hybrid Automata

This paper introduces Cancer Hybrid Automata (CHAs), a formalism to model the progression of cancers through discrete phenotypes. The classification of cancer progression using discrete states like stages and hallmarks has become common in the biology literature, but primarily as an organizing principle, and not as an executable formalism. The precise computational model developed here aims to exploit this untapped potential, namely, through automatic verification of progression models (e.g., consistency, causal connections, etc.), classification of unreachable or unstable states and computer-generated (individualized or universal) therapy plans. The paper builds on a phenomenological approach, and as such does not need to assume a model for the biochemistry of the underlying natural progression. Rather, it abstractly models transition timings between states as well as the effects of drugs and clinical tests, and thus allows formalization of temporal statements about the progression as well as notions of timed therapies. The model proposed here is ultimately based on hybrid automata, and we show how existing controller synthesis algorithms can be generalized to CHA models, so that therapies can be generated automatically. Throughout this paper we use cancer hallmarks to represent the discrete states through which cancer progresses, but other notions of discretely or continuously varying state formalisms could also be used to derive similar therapies.

eess.SY↗

arXiv2012

The Temporal Logic of Causal Structures

Computational analysis of time-course data with an underlying causal structure is needed in a variety of domains, including neural spike trains, stock price movements, and gene expression levels. However, it can be challenging to determine from just the numerical time course data alone what is coordinating the visible processes, to separate the underlying prima facie causes into genuine and spurious causes and to do so with a feasible computational complexity. For this purpose, we have been developing a novel algorithm based on a framework that combines notions of causality in philosophy with algorithmic approaches built on model checking and statistical techniques for multiple hypotheses testing. The causal relationships are described in terms of temporal logic formulae, reframing the inference problem in terms of model checking. The logic used, PCTL, allows description of both the time between cause and effect and the probability of this relationship being observed. We show that equipped with these causal formulae with their associated probabilities we may compute the average impact a cause makes to its effect and then discover statistically significant causes through the concepts of multiple hypothesis testing (treating each causal relationship as a hypothesis), and false discovery control. By exploring a well-chosen family of potentially all significant hypotheses with reasonably minimal description length, it is possible to tame the algorithm's computational complexity while exploring the nearly complete search-space of all prima facie causes. We have tested these ideas in a number of domains and illustrate them here with two examples.

cs.AI↗