arXiv subjects

Kartik Singhal

Publications and source records attributed to Kartik Singhal.

13 recordsLinked to original sources

arXiv2026

pVACtools v6: A comprehensive suite for neoantigen prediction, visualization, and therapy design

With the rise of checkpoint blockade therapies and neoantigen-based vaccines reaching later-stage trials, there is a growing need for computational tools to identify and prioritize neoantigens. pVACtools, initially introduced in 2016, is an open-source informatic suite designed to support basic and translational neoantigen research. pVACtools assists prediction, prioritization, and visualization of neoantigens, as well as design of neoantigen-based therapies. We describe several major advances to pVACtools since the last update: (1) expanded neoantigen quality and safety assessment features, including support for peptide presentation scoring, immunogenicity prediction, anchor residue analysis, reference proteome similarity, percentile score calculation; (2) addition of pVACsplice, a new tool for predicting neoantigens from tumor-specific cis-splicing mutations; (3) addition of pVACbind, a flexible tool that supports noncanonical neoantigen sources; (4) improvement in neoantigen selection strategies; (5) a substantially improved pVACvector algorithm that achieves higher DNA/mRNA vector vaccine design success rates with shorter runtimes; (6) new utilities to support synthetic long peptide vaccine design; (7) extended prediction support for many non-human species; and (8) addition of pVACcompare, a tool to support comparison between two pVACseq results. Together, these updates reinforce pVACtools as the field's most comprehensive toolkit for neoantigen research, from basic discovery to the design and execution of personalized cancer vaccine clinical trials.

q-bio.QM↗

arXiv2025

ImmunoNX: a robust bioinformatics workflow to support personalized neoantigen vaccine trials

Personalized neoantigen vaccines represent a promising immunotherapy approach that harnesses tumor-specific antigens to stimulate anti-tumor immune responses. However, the design of these vaccines requires sophisticated computational workflows to predict and prioritize neoantigen candidates from patient sequencing data, coupled with rigorous review to ensure candidate quality. While numerous computational tools exist for neoantigen prediction, to our knowledge, there are no established protocols detailing the complete process from raw sequencing data through systematic candidate selection. Here, we present ImmunoNX (Immunogenomics Neoantigen eXplorer), an end-to-end protocol for neoantigen prediction and vaccine design that has supported over 185 patients across 11 clinical trials. The workflow integrates tumor DNA/RNA and matched normal DNA sequencing data through a computational pipeline built with Workflow Definition Language (WDL) and executed via Cromwell on Google Cloud Platform. ImmunoNX employs consensus-based variant calling, in-silico HLA typing, and pVACtools for neoantigen prediction. Additionally, we describe a two-stage immunogenomics review process with prioritization of neoantigen candidates, enabled by pVACview, followed by manual assessment of variants using the Integrative Genomics Viewer (IGV). This workflow enables vaccine design in under three months. We demonstrate the protocol using the HCC1395 breast cancer cell line dataset, identifying 78 high-confidence neoantigen candidates from 322 initial predictions. Although demonstrated here for vaccine development, this workflow can be adapted for diverse neoantigen therapies and experiments. Therefore, this protocol provides the research community with a reproducible, version-controlled framework for designing personalized neoantigen vaccines, supported by detailed documentation, example datasets, and open-source code.

q-bio.GN↗

arXiv2025

Certified randomness amplification by dynamically probing remote random quantum states

Cryptography depends on truly unpredictable numbers, but physical sources emit biased or correlated bits. Quantum mechanics enables the amplification of imperfect randomness into nearly perfect randomness, but prior demonstrations have required physically co-located, loophole-free Bell tests, constraining the feasibility of remote operation. Here we realize certified randomness amplification across a network by dynamically probing large, entangled quantum states on Quantinuum's 98-qubit Helios trapped-ion quantum processor. Our protocol is secure even if the remote device acts maliciously or is compromised by an intercepting adversary, provided the samples are generated quickly enough to preclude classical simulation of the quantum circuits. We stream quantum gates in real time to the quantum processor, maintain quantum state coherence for $\approx 0.9$ seconds, and then reveal the measurement bases to the quantum processor only milliseconds before measurement. This limits the time for classical spoofing to 30 ms and constrains the location of hypothetical adversaries to a $4{,}500$ km radius. We achieve a fidelity of 0.586 on random circuits with 64 qubits and 276 two-qubit gates, enabling the amplification of realistic imperfect randomness with a low entropy rate into nearly perfect randomness.

quant-ph↗

arXiv2025

Realization of a Quantum Streaming Algorithm on Long-lived Trapped-ion Qubits

Large classical datasets are often processed in the streaming model, with data arriving one item at a time. In this model, quantum algorithms have been shown to offer an unconditional exponential advantage in space. However, experimentally implementing such streaming algorithms requires qubits that remain coherent while interacting with an external data stream. In this work, we realize such a data-streaming model using Quantinuum Helios trapped-ion quantum computer with long-lived qubits that communicate with an external server. We implement a quantum pair sketch, which is the primitive underlying many quantum streaming algorithms, and use it to solve Hidden Matching, a problem known to exhibit a theoretical exponential quantum advantage in space. Furthermore, we compile the quantum streaming algorithm to fault-tolerant quantum architectures based on surface and bivariate bicycle codes and show that the quantum space advantage persists even with the overheads of fault-tolerance.

quant-ph↗

arXiv2025

Imperative Quantum Programming with Ownership and Borrowing in Guppy

Linear types enforce no-cloning and no-deleting theorems in functional quantum programming. However, in imperative quantum programming, they have not gained widespread adoption. This work aims to develop a quantum type system that combines ergonomic linear typing with imperative semantics and maintains safety guarantees. All ideas presented here have been implemented in Quantinuum's Guppy programming language.

cs.PL↗

arXiv2025

GUPPY: Pythonic Quantum-Classical Programming

We present ongoing work on Guppy, a domain-specific language embedded in Python that allows users to write high-level hybrid quantum programs with complex control flow in Pythonic syntax, aiming to run them on actual quantum hardware.

cs.PL↗

arXiv2024

ConceptSearch: Towards Efficient Program Search Using LLMs for Abstraction and Reasoning Corpus (ARC)

The Abstraction and Reasoning Corpus (ARC) poses a significant challenge to artificial intelligence, demanding broad generalization and few-shot learning capabilities that remain elusive for current deep learning methods, including large language models (LLMs). While LLMs excel in program synthesis, their direct application to ARC yields limited success. To address this, we introduce ConceptSearch, a novel function-search algorithm that leverages LLMs for program generation and employs a concept-based scoring method to guide the search efficiently. Unlike simplistic pixel-based metrics like Hamming distance, ConceptSearch evaluates programs on their ability to capture the underlying transformation concept reflected in the input-output examples. We explore three scoring functions: Hamming distance, a CNN-based scoring function, and an LLM-based natural language scoring function. Experimental results demonstrate the effectiveness of ConceptSearch, achieving a significant performance improvement over direct prompting with GPT-4. Moreover, our novel concept-based scoring exhibits up to 30% greater efficiency compared to Hamming distance, measured in terms of the number of iterations required to reach the correct solution. These findings highlight the potential of LLM-driven program search when integrated with concept-based guidance for tackling challenging generalization problems like ARC.

cs.LG↗

arXiv2023

Q# as a Quantum Algorithmic Language

Q# is a standalone domain-specific programming language from Microsoft for writing and running quantum programs. Like most industrial languages, it was designed without a formal specification, which can naturally lead to ambiguity in its interpretation. We aim to provide a formal language definition for Q#, placing the language on a solid mathematical foundation and enabling further evolution of its design and type system. This paper presents $λ$-Q#, an idealized version of Q# that illustrates how we may view Q# as a quantum Algol (algorithmic language). We show the safety properties enforced by $λ$-Q#'s type system and present its equational semantics based on a fully complete algebraic theory by Staton.

cs.PL↗

arXiv2021

Quantum Hoare Type Theory

As quantum computers become real, it is high time we come up with effective techniques that help programmers write correct quantum programs. Inspired by Hoare Type Theory in classical computing, we propose Quantum Hoare Type Theory (QHTT), in which precise specifications about the modification to the quantum state can be provided within the type of computation. These specifications within a Hoare type are given in the form of Hoare-logic style pre- and postconditions following the propositions-as-types principle. The type-checking process verifies that the implementation conforms to the provided specification. QHTT has the potential to be a unified system for programming, specifying, and reasoning about quantum programs.

cs.PL↗

arXiv2021

Gottesman Types for Quantum Programs

The Heisenberg representation of quantum operators provides a powerful technique for reasoning about quantum circuits, albeit those restricted to the common (non-universal) Clifford set H, S and CNOT. The Gottesman-Knill theorem showed that we can use this representation to efficiently simulate Clifford circuits. We show that Gottesman's semantics for quantum programs can be treated as a type system, allowing us to efficiently characterize a common subset of quantum programs. We also show that it can be extended beyond the Clifford set to partially characterize a broad range of programs. We apply these types to reason about separable states and the superdense coding algorithm.

cs.LO↗

arXiv2021

Quantum Hoare Type Theory: Extended Abstract

As quantum computers become real, it is high time we come up with effective techniques that help programmers write correct quantum programs. In classical computing, formal verification and sound static type systems prevent several classes of bugs from being introduced. There is a need for similar techniques in the quantum regime. Inspired by Hoare Type Theory in the classical paradigm, we propose Quantum Hoare Types by extending the Quantum IO Monad by indexing it with pre- and post-conditions that serve as program specifications. In this paper, we introduce Quantum Hoare Type Theory (QHTT), present its syntax and typing rules, and demonstrate its effectiveness with the help of examples. QHTT has the potential to be a unified system for programming, specifying, and reasoning about quantum programs. This is a work in progress.

cs.PL↗

arXiv2021

Hoare meets Heisenberg: A Lightweight Logic for Quantum Programs

We show that Gottesman's (1998) semantics for Clifford circuits based on the Heisenberg representation gives rise to a lightweight Hoare-like logic for efficiently characterizing a common subset of quantum programs. Our applications include (i) certifying whether auxiliary qubits can be safely disposed of, (ii) determining if a system is separable across a given bipartition, (iii) checking the transversality of a gate with respect to a given stabilizer code, and (iv) computing post-measurement states for computational basis measurements. Further, this logic is extended to accommodate universal quantum computing by deriving Hoare triples for the $T$-gate, multiply-controlled unitaries such as the Toffoli gate, and some gate injection circuits that use associated magic states. A number of interesting results emerge from this logic, including a lower bound on the number of $T$ gates necessary to perform a multiply-controlled $Z$ gate.

quant-ph↗

arXiv2015

Predicting Small Group Accretion in Social Networks: A topology based incremental approach

Small Group evolution has been of central importance in social sciences and also in the industry for understanding dynamics of team formation. While most of research works studying groups deal at a macro level with evolution of arbitrary size communities, in this paper we restrict ourselves to studying evolution of small group (size $\leq20$) which is governed by contrasting sociological phenomenon. Given a previous history of group collaboration between a set of actors, we address the problem of predicting likely future group collaborations. Unfortunately, predicting groups requires choosing from $n \choose r$ possibilities (where $r$ is group size and $n$ is total number of actors), which becomes computationally intractable as group size increases. However, our statistical analysis of a real world dataset has shown that two processes: an external actor joining an existing group (incremental accretion (IA)) or collaborating with a subset of actors of an exiting group (subgroup accretion (SA)), are largely responsible for future group formation. This helps to drastically reduce the $n\choose r$ possibilities. We therefore, model the attachment of a group for different actors outside this group. In this paper, we have built three topology based prediction models to study these phenomena. The performance of these models is evaluated using extensive experiments over DBLP dataset. Our prediction results shows that the proposed models are significantly useful for future group predictions both for IA and SA.

cs.SI↗