BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Biomedical Mathematics Group - ECPv6.16.2//NONSGML v1.0//EN
CALSCALE:GREGORIAN
METHOD:PUBLISH
X-WR-CALNAME:Biomedical Mathematics Group
X-ORIGINAL-URL:https://www.ibs.re.kr/bimag
X-WR-CALDESC:Events for Biomedical Mathematics Group
REFRESH-INTERVAL;VALUE=DURATION:PT1H
X-Robots-Tag:noindex
X-PUBLISHED-TTL:PT1H
BEGIN:VTIMEZONE
TZID:Asia/Seoul
BEGIN:STANDARD
TZOFFSETFROM:+0900
TZOFFSETTO:+0900
TZNAME:KST
DTSTART:20250101T000000
END:STANDARD
END:VTIMEZONE
BEGIN:VEVENT
DTSTART;TZID=Asia/Seoul:20260619T100000
DTEND;TZID=Asia/Seoul:20260619T120000
DTSTAMP:20260528T032436
CREATED:20260527T140141Z
LAST-MODIFIED:20260527T140141Z
UID:12539-1781863200-1781870400@www.ibs.re.kr
SUMMARY:A Metabolism-Informed Neural Network Identifies Pathways Influencing the Potency and Toxicity of Antimicrobial Combinations - Se Jun Ahn
DESCRIPTION:In this talk\, we discuss the paper “A Metabolism-Informed Neural Network Identifies Pathways Influencing the Potency and Toxicity of Antimicrobial Combinations” by Harkirat Sigh Arora et al.\, npj drug discovery\, 2026. \nAbstract: \nAntimicrobial resistance poses a major global threat\, driven by diminishing efficacy of current treatments and limited new therapies. Combination therapy with existing drugs offers a promising solution\, yet current empirical screening methods are expensive and often lead to suboptimal efficacy and inadvertent toxicity. We introduce CALMA\, a computational framework that quantitatively analyzes the potency-toxicity landscape of multi-drug combinations. Integrating genome-scale metabolic modeling with a neural network that reflects metabolic subsystems\, CALMA enhances interpretability and prioritizes pathways influencing drug interactions. The incorporation of metabolic architecture in the neural network leads to over 92% reduction in model parameters\, enabling it to learn generalizable mechanistic signals and reducing the experimental search space of optimal combinations by 97%. CALMA identified promising antimicrobial combinations against Escherichia coli and Mycobacterium tuberculosis that were antagonistic for kidney and liver toxicity and uncovered the nucleotide salvage pathway as a selective influencer of toxicity\, which was validated in vitro. Mining of health records of over 400\,000 patients showed reduced frequency of kidney side-effects in patients taking a vancomycin combination identified by CALMA. CALMA provides a rational\, mechanistic approach to streamline combination treatment design.
URL:https://www.ibs.re.kr/bimag/event/a-metabolism-informed-neural-network-identifies-pathways-influencing-the-potency-and-toxicity-of-antimicrobial-combinations-se-jun-ahn/
LOCATION:B232 Seminar Room\, IBS\, 55 Expo-ro Yuseong-gu\, Daejeon\, Daejeon\, 34126\, Korea\, Republic of
CATEGORIES:Journal Club
ORGANIZER;CN="Jae Kyoung Kim":MAILTO:jaekkim@kaist.ac.kr
END:VEVENT
END:VCALENDAR