:root {
    --primary-color: #0056b3;
    --text-color: #333;
    --text-muted: #666;
    --border-color: #e5e7eb;
    --bg-color: #f9fafb;
    --card-bg: #ffffff;
    --font-family: 'Inter', -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, "Helvetica Neue", Arial, sans-serif;
}

* { box-sizing: border-box; }

body {
    font-family: var(--font-family);
    margin: 0;
    padding: 0;
    background-color: var(--bg-color);
    color: var(--text-color);
    line-height: 1.6;
}

.container {
    max-width: 1100px;
    margin: 0 auto;
    padding: 0 24px;
}

/* ==================== Header ==================== */
header {
    display: flex;
    justify-content: space-between;
    align-items: center;
    padding: 16px 0;
    border-bottom: 1px solid var(--border-color);
}

.logo {
    font-size: 1.25rem;
    font-weight: 700;
    color: var(--primary-color);
}

nav a {
    margin-left: 20px;
    text-decoration: none;
    color: var(--text-muted);
    font-weight: 500;
    font-size: 0.875rem;
}

nav a:hover { color: var(--primary-color); }

.nav-link {
    text-decoration: none;
    border: 1px solid var(--border-color);
    border-radius: 6px;
    padding: 6px 14px;
    font-family: var(--font-family);
    font-size: 0.875rem;
    font-weight: 500;
    color: var(--text-muted);
    transition: all 0.2s;
}

.nav-link:hover {
    border-color: var(--primary-color);
    color: var(--primary-color);
}

/* ==================== Changelog ==================== */
.changelog-page { max-width: 800px; margin: 0 auto; }
.changelog-page h1 { font-size: 2rem; color: var(--primary-color); margin-bottom: 4px; }
.changelog-subtitle { color: var(--text-muted); margin-bottom: 40px; font-size: 1rem; }
.changelog-version { margin-bottom: 48px; }

.version-header {
    display: flex;
    align-items: baseline;
    gap: 16px;
    margin-bottom: 24px;
    padding-bottom: 12px;
    border-bottom: 2px solid var(--primary-color);
}

.version-header h2 { margin: 0; font-size: 1.5rem; }
.version-date { color: var(--text-muted); font-size: 0.9rem; }
.changelog-section { margin-bottom: 20px; }
.changelog-section h3 { display: flex; align-items: center; gap: 10px; margin: 0 0 8px 0; font-size: 1rem; font-weight: 600; }
.changelog-section ul { margin: 0; padding-left: 24px; color: #495057; }
.changelog-section li { padding: 3px 0; font-size: 0.925rem; line-height: 1.5; }
.changelog-section code { background: #f3f4f6; padding: 1px 6px; border-radius: 3px; font-size: 0.85em; }
.changelog-tag { font-size: 0.7rem; font-weight: 600; text-transform: uppercase; padding: 2px 8px; border-radius: 4px; flex-shrink: 0; }
.tag-new { background: #d4edda; color: #155724; }
.tag-improved { background: #cce5ff; color: #004085; }
.tag-fixed { background: #fff3cd; color: #856404; }

/* ==================== Main / Tabs ==================== */
main {
    flex: 1;
    padding: 20px 0;
}

.main-tabs {
    display: flex;
    gap: 0;
    border-bottom: 1px solid var(--border-color);
    margin-bottom: 16px;
}

.main-tab {
    padding: 10px 20px;
    font-size: 0.9rem;
    font-weight: 600;
    font-family: var(--font-family);
    background: none;
    border: none;
    border-bottom: 2px solid transparent;
    color: var(--text-muted);
    cursor: pointer;
    transition: all 0.15s;
    margin-bottom: -1px;
}

.main-tab:hover { color: var(--primary-color); }

.main-tab.active {
    color: var(--primary-color);
    border-bottom-color: var(--primary-color);
}

.tab-panel { display: none; }
.tab-panel.active { display: block; }

/* ==================== Panel Header ==================== */
.panel-header {
    margin-bottom: 16px;
}

.panel-title {
    font-size: 1rem;
    font-weight: 700;
    margin: 0 0 2px 0;
    color: var(--text-color);
}

.panel-subtitle {
    color: var(--text-muted);
    font-size: 0.85rem;
    margin: 0;
}

/* ==================== Search Row ==================== */
.input-row {
    display: flex;
    gap: 8px;
    margin-bottom: 6px;
    align-items: center;
}

#variant-input {
    padding: 8px 12px;
    font-size: 0.9rem;
    border: 1px solid var(--border-color);
    border-radius: 6px;
    width: 300px;
    font-family: var(--font-family);
    transition: border-color 0.2s;
}

#variant-input:focus {
    outline: none;
    border-color: var(--primary-color);
}

.examples {
    font-size: 0.8rem;
    color: var(--text-muted);
    margin-bottom: 16px;
    padding-bottom: 16px;
    border-bottom: 1px solid var(--border-color);
}

.example-btn {
    background: none;
    border: none;
    color: var(--primary-color);
    cursor: pointer;
    text-decoration: underline;
    padding: 0 4px;
    font-size: 0.8rem;
}

/* ==================== Options Panel ==================== */
/* ==================== Two-Column Layout ==================== */
.tab-layout {
    display: flex;
    gap: 24px;
    align-items: flex-start;
}

.tab-layout .analysis-options {
    flex: 1;
    min-width: 0;
}

.info-panel {
    width: 300px;
    flex-shrink: 0;
    padding: 20px;
    background: var(--card-bg);
    border: 1px solid var(--border-color);
    border-radius: 8px;
}

.info-panel h3 {
    font-size: 0.8rem;
    font-weight: 700;
    text-transform: uppercase;
    letter-spacing: 0.03em;
    color: var(--text-color);
    margin: 0 0 6px 0;
}

.info-panel h3:not(:first-child) {
    margin-top: 14px;
}

.info-panel p {
    font-size: 0.82rem;
    color: var(--text-muted);
    line-height: 1.5;
    margin: 0 0 4px 0;
}

.info-panel ul {
    margin: 0;
    padding-left: 16px;
    font-size: 0.82rem;
    color: var(--text-muted);
    line-height: 1.5;
}

.info-panel li {
    margin-bottom: 4px;
}

.info-panel strong {
    color: var(--text-color);
}

.analysis-options {
    background: var(--card-bg);
    border-radius: 8px;
    padding: 20px;
    margin-bottom: 16px;
    border: 1px solid var(--border-color);
}

.options-row {
    display: flex;
    gap: 40px;
    flex-wrap: wrap;
    align-items: flex-start;
}

.control-group {
    display: flex;
    flex-direction: column;
    gap: 4px;
}

.control-group > label {
    font-weight: 600;
    font-size: 0.85rem;
    color: var(--text-color);
    text-transform: uppercase;
    letter-spacing: 0.03em;
}

.control-group small {
    color: var(--text-muted);
    font-size: 0.8rem;
}

.tissue-search {
    padding: 7px 10px;
    font-size: 0.85rem;
    border: 1px solid var(--border-color);
    border-radius: 6px 6px 0 0;
    font-family: var(--font-family);
    width: 220px;
    border-bottom: none;
    margin-bottom: -4px;
}

.tissue-search:focus {
    outline: none;
    border-color: var(--primary-color);
}

.tissue-dropdown {
    width: 220px;
    height: 130px;
    padding: 4px;
    border: 1px solid var(--border-color);
    border-radius: 0 0 6px 6px;
    font-size: 0.82rem;
    font-family: var(--font-family);
}

.selected-tags {
    display: flex;
    flex-wrap: wrap;
    gap: 4px;
    margin-top: 4px;
}


.checkbox-group-vertical {
    display: flex;
    flex-direction: column;
    gap: 6px;
    margin-top: 2px;
}

.checkbox-group-vertical label {
    font-weight: 400;
    display: flex;
    align-items: center;
    gap: 6px;
    cursor: pointer;
    font-size: 0.9rem;
}

.analyze-btn-container {
    margin-top: 16px;
}

.action-btn {
    padding: 8px 20px;
    font-size: 0.85rem;
    background-color: var(--primary-color);
    color: white;
    border: none;
    border-radius: 6px;
    cursor: pointer;
    font-weight: 600;
    font-family: var(--font-family);
    transition: background-color 0.2s;
}

.action-btn:hover { background-color: #004494; }
.action-btn:disabled { opacity: 0.6; cursor: not-allowed; }

.action-btn.loading::after {
    content: '';
    display: inline-block;
    width: 18px;
    height: 18px;
    border: 2px solid rgba(255, 255, 255, 0.3);
    border-top-color: #fff;
    border-radius: 50%;
    animation: spin 0.8s linear infinite;
}

@keyframes spin { to { transform: rotate(360deg); } }

/* ==================== Shared: selects & inputs ==================== */
.control-group select,
.ism-field select {
    padding: 8px 10px;
    font-size: 0.9rem;
    border: 1px solid var(--border-color);
    border-radius: 6px;
    background-color: white;
    cursor: pointer;
    font-family: var(--font-family);
}

.control-group select:focus,
.ism-field select:focus {
    outline: none;
    border-color: var(--primary-color);
}

/* ==================== Loading ==================== */
#loading,
#ism-loading {
    text-align: center;
    padding: 40px;
    color: var(--text-muted);
    font-size: 0.95rem;
}

#loading::before {
    content: '';
    display: block;
    width: 180px;
    height: 3px;
    margin: 0 auto 12px;
    background-color: var(--border-color);
    border-radius: 2px;
}

#loading::after {
    content: '';
    display: block;
    width: 180px;
    height: 3px;
    margin: -15px auto 12px;
    background: linear-gradient(90deg, transparent, var(--primary-color), transparent);
    border-radius: 2px;
    animation: loading-slide 1.5s ease-in-out infinite;
}

@keyframes loading-slide {
    0% { transform: translateX(-100%); }
    100% { transform: translateX(100%); }
}

/* ==================== Results / Report ==================== */
.results-section {
    background: var(--card-bg);
    border-radius: 8px;
    padding: 24px;
    border: 1px solid var(--border-color);
}

.results-section.hidden { display: none; }
.hidden { display: none !important; }

.report-section {
    padding: 20px 0;
    margin-bottom: 0;
    border-bottom: 1px solid var(--border-color);
}

.report-section:last-child {
    border-bottom: none;
}

.report-section h3 {
    margin: 0 0 16px 0;
    color: var(--text-color);
    font-size: 1rem;
    font-weight: 600;
}

/* ==================== Gene Info ==================== */
.gene-info-section { padding-top: 0; }

.gene-info-card {
    display: flex;
    align-items: center;
    gap: 10px;
}

.gene-primary {
    display: flex;
    align-items: center;
    gap: 12px;
}

.gene-label {
    color: var(--text-muted);
    font-size: 0.85rem;
}

.gene-name-large {
    font-size: 1.5rem;
    font-weight: 700;
    color: var(--primary-color);
}

/* ==================== Expression Card ==================== */
.expression-card {
    border-radius: 6px;
    border: 1px solid var(--border-color);
}

.expression-card-body {
    padding: 16px;
}

.score-main {
    text-align: center;
    margin-bottom: 12px;
    padding-bottom: 12px;
    border-bottom: 1px solid var(--border-color);
}

.score-value {
    display: block;
    font-size: 1.8rem;
    font-weight: 700;
    color: var(--text-color);
}

.score-label {
    display: block;
    font-size: 0.8rem;
    color: var(--text-muted);
    margin-top: 2px;
}

.score-details {
    display: flex;
    flex-direction: column;
    gap: 0;
}

.detail-row {
    display: flex;
    justify-content: space-between;
    align-items: center;
    padding: 6px 0;
}

.detail-label {
    color: var(--text-muted);
    font-size: 0.85rem;
}

.detail-value {
    font-weight: 600;
    font-size: 0.85rem;
}

/* ==================== Tables ==================== */
.table-container { overflow-x: auto; }

table {
    width: 100%;
    border-collapse: collapse;
    margin-top: 12px;
    font-size: 0.875rem;
}

th, td {
    padding: 8px 12px;
    text-align: left;
    border-bottom: 1px solid var(--border-color);
}

th {
    font-weight: 600;
    color: var(--text-muted);
    font-size: 0.8rem;
    text-transform: uppercase;
    letter-spacing: 0.03em;
}

tr:last-child td { border-bottom: none; }

.clinical-table { width: 100%; border-collapse: collapse; }
.clinical-table th { text-transform: uppercase; font-size: 0.8rem; letter-spacing: 0.03em; }
.clinical-table td { padding: 8px 12px; border-bottom: 1px solid var(--border-color); }

.score-high { color: #b91c1c; font-weight: 700; }
.score-medium { color: #92400e; font-weight: 600; }

.value-decreased { color: #b91c1c; font-weight: 600; }
.value-increased { color: #15803d; font-weight: 600; }
.value-significant { color: var(--primary-color); font-weight: 600; }
.value-good { color: #15803d; font-weight: 600; }

/* ==================== Plots ==================== */
.plot-controls {
    display: flex;
    justify-content: flex-end;
    margin-bottom: 12px;
}

.zoom-control {
    display: flex;
    align-items: center;
    gap: 8px;
}

.zoom-control label {
    font-size: 0.85rem;
    font-weight: 500;
    color: var(--text-muted);
}

.zoom-control select {
    padding: 6px 10px;
    font-size: 0.85rem;
    border: 1px solid var(--border-color);
    border-radius: 4px;
    background-color: white;
    min-width: 140px;
}

.sashimi-plot-container {
    text-align: center;
}

.plot-description {
    color: var(--text-muted);
    font-size: 0.85rem;
    margin-bottom: 12px;
}

.sashimi-plot {
    max-width: 100%;
    height: auto;
    border: 1px solid var(--border-color);
    border-radius: 6px;
}

#sashimi-loading {
    text-align: center;
    padding: 40px;
    color: var(--text-muted);
}

.no-data {
    color: var(--text-muted);
    font-style: italic;
}

/* ==================== Interpretation Cards ==================== */
.junction-change-card,
.splice-site-card {
    border-radius: 6px;
    margin-bottom: 8px;
    border: 1px solid var(--border-color);
    overflow: hidden;
}

.junction-change-card.junction-loss,
.splice-site-card.splice-loss {
    border-left: 3px solid #b91c1c;
}

.junction-change-card.junction-gain,
.splice-site-card.splice-gain {
    border-left: 3px solid #15803d;
}

.junction-card-header,
.splice-site-card-header {
    display: flex;
    align-items: center;
    gap: 10px;
    padding: 10px 14px;
    flex-wrap: wrap;
}

.junction-badge {
    display: inline-block;
    padding: 1px 8px;
    border-radius: 10px;
    font-size: 0.7rem;
    font-weight: 700;
    letter-spacing: 0.5px;
    color: #fff;
}

.badge-loss { background-color: #b91c1c; }
.badge-gain { background-color: #15803d; }

.junction-title {
    font-weight: 600;
    font-size: 0.9rem;
    font-family: 'Courier New', monospace;
}

.junction-values {
    margin-left: auto;
    font-weight: 600;
    font-size: 0.85rem;
    color: var(--text-muted);
    font-family: 'Courier New', monospace;
}

.splice-site-title { font-weight: 600; font-size: 0.9rem; }

.splice-site-score {
    margin-left: auto;
    font-weight: 600;
    font-size: 0.85rem;
    color: var(--text-muted);
    font-family: 'Courier New', monospace;
}

.junction-card-body,
.splice-site-card-body {
    padding: 10px 14px;
}

.junction-coords,
.splice-site-position {
    font-size: 0.8rem;
    color: var(--text-muted);
    margin-bottom: 4px;
}

.junction-description,
.splice-site-description {
    font-size: 0.9rem;
    line-height: 1.5;
}

.junction-relationship {
    margin-top: 6px;
    font-size: 0.85rem;
    color: var(--primary-color);
}

.severity-badge {
    display: inline-block;
    padding: 1px 8px;
    border-radius: 10px;
    font-size: 0.7rem;
    font-weight: 700;
    letter-spacing: 0.5px;
    color: #fff;
}

.severity-strong { background-color: #b91c1c; }
.severity-significant { background-color: #d97706; }
.severity-moderate { background-color: #ca8a04; color: #fff; }
.severity-mild { background-color: #6b7280; }

/* ==================== Summary ==================== */
.summary-section { border-bottom: none; }

.summary-box {
    border-left: 3px solid var(--primary-color);
    padding: 12px 16px;
    background: #f0f7ff;
    border-radius: 0 6px 6px 0;
}

.summary-box p {
    margin: 0;
    font-size: 0.9rem;
    line-height: 1.6;
}

/* ==================== Error ==================== */
.error {
    color: #b91c1c;
    background-color: #fef2f2;
    border: 1px solid #fecaca;
    padding: 12px 16px;
    border-radius: 6px;
    margin-bottom: 16px;
    font-size: 0.9rem;
}

/* ==================== ISM Form (Tab 2) ==================== */
.ism-form {
    display: flex;
    flex-direction: column;
    gap: 14px;
}

.ism-region-radios {
    display: flex;
    gap: 20px;
    margin-top: 4px;
}

.ism-region-label {
    font-weight: 400 !important;
    cursor: pointer;
    display: flex;
    align-items: center;
    gap: 6px;
    font-size: 0.9rem;
}

.ism-field-row {
    display: flex;
    gap: 16px;
    flex-wrap: wrap;
    align-items: flex-start;
}

.ism-field {
    display: flex;
    flex-direction: column;
    gap: 4px;
}

.ism-field label {
    font-weight: 500;
    font-size: 0.8rem;
    color: var(--text-muted);
    text-transform: uppercase;
    letter-spacing: 0.03em;
}

.ism-field input[type="text"],
.ism-field input[type="number"] {
    padding: 8px 12px;
    font-size: 0.9rem;
    border: 1px solid var(--border-color);
    border-radius: 6px;
    width: 140px;
    font-family: var(--font-family);
}

.ism-field input:focus {
    outline: none;
    border-color: var(--primary-color);
}

#ism-tissue-group .tissue-search,
#ism-tissue-group .tissue-dropdown {
    width: 220px;
}

.ism-span-indicator {
    margin-top: 8px;
    font-size: 0.85rem;
    color: var(--text-muted);
}

.span-ok { color: #15803d; font-weight: 600; }
.span-error { color: #b91c1c; font-weight: 600; }
#ism-span-error { color: #b91c1c; font-weight: 600; }

/* ==================== ISM Results ==================== */
.ism-tables-row {
    display: flex;
    gap: 24px;
    margin-top: 16px;
}

.ism-table-half {
    flex: 1;
    min-width: 0;
}

.ism-table-half h4 {
    margin: 0 0 8px 0;
    font-size: 0.85rem;
    font-weight: 600;
    color: var(--text-color);
    text-transform: uppercase;
    letter-spacing: 0.03em;
}

.ism-meta {
    color: var(--text-muted);
    font-size: 0.85rem;
    margin-top: 8px;
}

/* ==================== Footer ==================== */
footer {
    text-align: center;
    padding: 16px 0;
    color: var(--text-muted);
    font-size: 0.85rem;
    border-top: 1px solid var(--border-color);
    margin-top: 20px;
}

.footer-disclaimer {
    font-size: 0.8rem;
    color: #9ca3af;
    margin-bottom: 4px;
}

.footer-disclaimer a {
    color: #9ca3af;
    text-decoration: underline;
}

/* ==================== Responsive ==================== */
@media (max-width: 768px) {
    .tab-layout { flex-direction: column; }
    .info-panel { width: 100%; }
    .options-row { flex-direction: column; }
    .tissue-search, .tissue-dropdown { width: 100%; }
    #variant-input { width: 100%; max-width: 280px; }
    .input-row { flex-wrap: wrap; }
    .expression-card { max-width: 100%; }
    .ism-tables-row { flex-direction: column; }
    .ism-field-row { flex-direction: column; }
}